Variant 2-182741247-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018981.4(DNAJC10):c.1082G>A(p.Arg361His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,593,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DNAJC10
NM_018981.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

DNAJC10 (HGNC:24637): (DnaJ heat shock protein family (Hsp40) member C10) This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

DNAJC10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08932698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC10	NM_018981.4 linkuse as main transcript	c.1082G>A	p.Arg361His	missense_variant	13/24	ENST00000264065.12	NP_061854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC10	ENST00000264065.12 linkuse as main transcript	c.1082G>A	p.Arg361His	missense_variant	13/24	1	NM_018981.4	ENSP00000264065	P1	Q8IXB1-1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

240226

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

130082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000156

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:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1441114

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

717084

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.000351

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

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

Jan 16, 2024

The c.1082G>A (p.R361H) alteration is located in exon 13 (coding exon 11) of the DNAJC10 gene. This alteration results from a G to A substitution at nucleotide position 1082, causing the arginine (R) at amino acid position 361 to be replaced by a histidine (H). 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

0.067

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0030

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

.;N

MutationTaster

Benign

0.88

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.029

Sift

Benign

0.21

.;T

Sift4G

Benign

0.34

T;T

Polyphen

0.087

B;B

Vest4

0.22

MutPred

0.51

.;Loss of stability (P = 0.1258);

MVP

0.28

MPC

0.078

ClinPred

0.18

GERP RS

3.9

Varity_R

0.043

gMVP

0.50

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