NM_058246.4:c.801G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_058246.4(DNAJB6):c.801G>T(p.Ser267Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S267S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAJB6
NM_058246.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.06

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 7-157409904-G-T is Benign according to our data. Variant chr7-157409904-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 538669.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.06 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB6	NM_058246.4	MANE Select	c.801G>T	p.Ser267Ser	synonymous	Exon 9 of 10	NP_490647.1
	DNAJB6	NM_001363676.1		c.456G>T	p.Ser152Ser	synonymous	Exon 6 of 7	NP_001350605.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAJB6	ENST00000262177.9	TSL:1 MANE Select	c.801G>T	p.Ser267Ser	synonymous	Exon 9 of 10	ENSP00000262177.4
DNAJB6	ENST00000459889.5	TSL:1	n.801G>T		non_coding_transcript_exon	Exon 9 of 10	ENSP00000488263.1
DNAJB6	ENST00000634080.1	TSL:2	c.801G>T	p.Ser267Ser	synonymous	Exon 8 of 8	ENSP00000488740.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000748

AC:

AN:

133630

AF XY:

0.0000138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000948

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1382336

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31462

American (AMR)

AF:

0.00

AC:

AN:

35616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25088

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35668

South Asian (SAS)

AF:

0.00

AC:

AN:

79054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077710

Other (OTH)

AF:

0.0000173

AC:

AN:

57644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Apr 21, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.044

(source)

DANN

Benign

0.72

PhyloP100

-3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over