7-157416065-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_058246.4(DNAJB6):c.948G>A(p.Ser316Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,613,898 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 5 hom. )

Consequence

DNAJB6
NM_058246.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.65

Publications

1 publications found

Variant links:

Genes affected

DNAJB6 (HGNC:14888): (DnaJ heat shock protein family (Hsp40) member B6) This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

DNAJB6 Gene-Disease associations (from GenCC):

muscular dystrophy, limb-girdle, autosomal dominant
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

DNAJB6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 7-157416065-G-A is Benign according to our data. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157416065-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 288447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000158 (24/152328) while in subpopulation SAS AF = 0.00476 (23/4828). AF 95% confidence interval is 0.00326. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB6	NM_058246.4 link	c.948G>A	p.Ser316Ser	synonymous_variant	Exon 10 of 10	ENST00000262177.9	NP_490647.1	O75190-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJB6	ENST00000262177.9 link	c.948G>A	p.Ser316Ser	synonymous_variant	Exon 10 of 10	1	NM_058246.4	ENSP00000262177.4	O75190-1
DNAJB6	ENST00000459889.5 link	n.*5471G>A		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000488263.1	A0A0J9YX62
DNAJB6	ENST00000459889.5 link	n.*5471G>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000488263.1	A0A0J9YX62
DNAJB6	ENST00000443280.5 link	c.603G>A	p.Ser201Ser	synonymous_variant	Exon 7 of 7	2		ENSP00000396267.1	E9PH18

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000410

AC:

103

AN:

251048

AF XY:

0.000545

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1461570

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

216

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00343

AC:

296

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111798

Other (OTH)

AF:

0.000232

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000158

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00476

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

Benign:2

Sep 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Jun 03, 2016

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Limb-Girdle Muscular Dystrophy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over