NM_058246.4:c.176-20A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058246.4(DNAJB6):c.176-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,612,064 control chromosomes in the GnomAD database, including 1,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 222 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1273 hom. )

Consequence

DNAJB6
NM_058246.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.66

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-157366482-A-G is Benign according to our data. Variant chr7-157366482-A-G is described in ClinVar as [Benign]. Clinvar id is 262305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB6	NM_058246.4 link	c.176-20A>G		intron_variant	Intron 3 of 9	ENST00000262177.9	NP_490647.1	O75190-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB6	ENST00000262177.9 link	c.176-20A>G		intron_variant	Intron 3 of 9	1	NM_058246.4	ENSP00000262177.4		O75190-1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7522

AN:

152152

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0365

AC:

9154

AN:

251076

AF XY:

0.0361

show subpopulations

Gnomad AFR exome

AF:

0.0814

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.0145

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0395

GnomAD4 exome

AF:

0.0391

AC:

57150

AN:

1459794

Hom.:

1273

Cov.:

AF XY:

0.0387

AC XY:

28098

AN XY:

726308

show subpopulations

African (AFR)

AF:

0.0786

AC:

2626

AN:

33412

American (AMR)

AF:

0.0219

AC:

979

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

368

AN:

26126

East Asian (EAS)

AF:

0.0112

AC:

444

AN:

39660

South Asian (SAS)

AF:

0.0301

AC:

2591

AN:

86126

European-Finnish (FIN)

AF:

0.0430

AC:

2294

AN:

53324

Middle Eastern (MID)

AF:

0.0248

AC:

143

AN:

5766

European-Non Finnish (NFE)

AF:

0.0409

AC:

45430

AN:

1110384

Other (OTH)

AF:

0.0377

AC:

2275

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

2607

5213

7820

10426

13033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0495

AC:

7532

AN:

152270

Hom.:

222

Cov.:

AF XY:

0.0483

AC XY:

3598

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0802

AC:

3334

AN:

41560

American (AMR)

AF:

0.0320

AC:

489

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.0162

AC:

AN:

5180

South Asian (SAS)

AF:

0.0288

AC:

139

AN:

4822

European-Finnish (FIN)

AF:

0.0393

AC:

417

AN:

10602

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0418

AC:

2843

AN:

68018

Other (OTH)

AF:

0.0488

AC:

103

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

371

742

1113

1484

1855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0426

Hom.:

Bravo

AF:

0.0493

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 29, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.82

CADD

Benign

1.9

(source)

DANN

Benign

0.39

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_058246.4:c.176-20A>G

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