chr3-132446334-A-T

Position:

• chr3-132446334-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000260818.11(DNAJC13):​c.69-141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 572,856 control chromosomes in the GnomAD database, including 2,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (485 hom., cov: 32)
  • Exomes 𝑓: 0.088 (1862 hom.)
• Consequence: DNAJC13 ENST00000260818.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

Genes affected

DNAJC13 (HGNC:30343): (DnaJ heat shock protein family (Hsp40) member C13) This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson's disease. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-132446334-A-T is Benign according to our data. Variant chr3-132446334-A-T is described in ClinVar as [Benign]. Clinvar id is 1230045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.69-141A>T		intron_variant		ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.69-141A>T		intron_variant			NP_001316055.1
DNAJC13	XM_047447819.1	c.69-141A>T		intron_variant			XP_047303775.1
DNAJC13	XM_047447820.1	c.69-141A>T		intron_variant			XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.69-141A>T		intron_variant		1	NM_015268.4	ENSP00000260818	P1
DNAJC13	ENST00000486798.5	n.134-141A>T		intron_variant, non_coding_transcript_variant		1
DNAJC13	ENST00000650455.1	c.69-141A>T		intron_variant, NMD_transcript_variant				ENSP00000496825

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10581 AN: 152058 Hom.: 484 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0785

GnomAD4 exome AF: 0.0881 AC: 37073 AN: 420680 Hom.: 1862 AF XY: 0.0895 AC XY: 20285 AN XY: 226696

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.0548

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.000418

Gnomad4 SAS exome AF: 0.0989

Gnomad4 FIN exome AF: 0.0902

Gnomad4 NFE exome AF: 0.0983

Gnomad4 OTH exome AF: 0.0821

GnomAD4 genome AF: 0.0696 AC: 10585 AN: 152176 Hom.: 485 Cov.: 32 AF XY: 0.0685 AC XY: 5100 AN XY: 74402

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0932

Gnomad4 FIN AF: 0.0899

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0855 Hom.: 82

Bravo AF: 0.0633

Asia WGS AF: 0.0360 AC: 126 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs1979848; hg19: chr3-132165178;