Variant chr13-95677333-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006260.5(DNAJC3):c.78C>T(p.Tyr26=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0034 in 1,598,302 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 36 hom. )

Consequence

DNAJC3
NM_006260.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

DNAJC3 (HGNC:9439): (DnaJ heat shock protein family (Hsp40) member C3) This gene encodes a protein with multiple tetratricopeptide repeat (TPR) motifs as well as the highly conserved J domain found in DNAJ chaperone family members. It is a member of the tetratricopeptide repeat family of proteins and acts as an inhibitor of the interferon-induced, dsRNA-activated protein kinase (PKR). [provided by RefSeq, Jul 2010]

DNAJC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 13-95677333-C-T is Benign according to our data. Variant chr13-95677333-C-T is described in ClinVar as [Benign]. Clinvar id is 710813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00241 (367/152298) while in subpopulation SAS AF= 0.0166 (80/4830). AF 95% confidence interval is 0.0136. There are 2 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC3	NM_006260.5 linkuse as main transcript	c.78C>T	p.Tyr26=	synonymous_variant	1/12	ENST00000602402.6	NP_006251.1
DNAJC3	XM_011521104.3 linkuse as main transcript	c.78C>T	p.Tyr26=	synonymous_variant	1/13		XP_011519406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC3	ENST00000602402.6 linkuse as main transcript	c.78C>T	p.Tyr26=	synonymous_variant	1/12	1	NM_006260.5	ENSP00000473631	P1
DNAJC3	ENST00000376795.6 linkuse as main transcript	c.78C>T	p.Tyr26=	synonymous_variant	1/11	5		ENSP00000365991

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

369

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00389

AC:

902

AN:

231960

Hom.:

AF XY:

0.00482

AC XY:

610

AN XY:

126434

show subpopulations

Gnomad AFR exome

AF:

0.000231

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00350

AC:

5063

AN:

1446004

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

2843

AN XY:

719372

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.00152

Gnomad4 EAS exome

AF:

0.0000267

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.000264

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152298

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

DNAJC3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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