Variant 16-4425910-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005147.6(DNAJA3):c.29T>G(p.Leu10Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,545,470 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

DNAJA3
NM_005147.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

DNAJA3 (HGNC:11808): (DnaJ heat shock protein family (Hsp40) member A3) This gene encodes a member of the DNAJ/Hsp40 protein family. DNAJ/Hsp40 proteins stimulate the ATPase activity of Hsp70 chaperones and play critical roles in protein folding, degradation, and multimeric complex assembly. The encoded protein is localized to mitochondria and mediates several cellular processes including proliferation, survival and apoptotic signal transduction. The encoded protein also plays a critical role in tumor suppression through interactions with oncogenic proteins including ErbB2 and the p53 tumor suppressor protein. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

DNAJA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04137653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNAJA3	NM_005147.6 linkuse as main transcript	c.29T>G	p.Leu10Trp	missense_variant	1/12	ENST00000262375.11
DNAJA3	NM_001135110.3 linkuse as main transcript	c.29T>G	p.Leu10Trp	missense_variant	1/11
DNAJA3	XM_047434875.1 linkuse as main transcript	c.29T>G	p.Leu10Trp	missense_variant	1/11
DNAJA3	NM_001286516.2 linkuse as main transcript	c.-82T>G		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA3	ENST00000262375.11 linkuse as main transcript	c.29T>G	p.Leu10Trp	missense_variant	1/12	1	NM_005147.6	P3	Q96EY1-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000950

AC:

AN:

147322

Hom.:

AF XY:

0.0000378

AC XY:

AN XY:

79334

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

101

AN:

1393298

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

687724

show subpopulations

Gnomad4 AFR exome

AF:

0.00261

Gnomad4 AMR exome

AF:

0.0000841

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:

0.0000102

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000618

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000706

ESP6500AA

AF:

0.00167

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000545

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 22, 2023

The c.29T>G (p.L10W) alteration is located in exon 1 (coding exon 1) of the DNAJA3 gene. This alteration results from a T to G substitution at nucleotide position 29, causing the leucine (L) at amino acid position 10 to be replaced by a tryptophan (W). 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

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.17

T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.85

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.53

MVP

0.91

MPC

0.31

ClinPred

0.11

GERP RS

5.9

Varity_R

0.35

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over