Variant 19-14516581-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006145.3(DNAJB1):c.677A>G(p.Gln226Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAJB1
NM_006145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85

Variant links:

Genes affected

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. 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. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

DNAJB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB1	NM_006145.3 linkuse as main transcript	c.677A>G	p.Gln226Arg	missense_variant	2/3	ENST00000254322.3	NP_006136.1	P25685-1Q6FHS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB1	ENST00000254322.3 linkuse as main transcript	c.677A>G	p.Gln226Arg	missense_variant	2/3	1	NM_006145.3	ENSP00000254322.1		P25685-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2023

The c.677A>G (p.Q226R) alteration is located in exon 2 (coding exon 2) of the DNAJB1 gene. This alteration results from a A to G substitution at nucleotide position 677, causing the glutamine (Q) at amino acid position 226 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Uncertain

0.036

MutationAssessor

Uncertain

2.4

M;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.9

D;D;.;.

REVEL

Uncertain

0.48

Sift

Benign

0.039

D;T;.;.

Sift4G

Benign

0.070

T;T;.;.

Polyphen

0.0070

B;.;.;.

Vest4

0.43

MutPred

0.46

Gain of catalytic residue at Q226 (P = 0.0891);.;.;.;

MVP

0.87

MPC

0.36

ClinPred

0.97

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

gMVP

0.64

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over