13-95722132-C-T

Variant names:

• chr13-95722132-C-T
• rs9302083
• NM_006260.5:c.194-1110C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006260.5(DNAJC3):​c.194-1110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,048 control chromosomes in the GnomAD database, including 28,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28618 hom., cov: 32)
• Consequence: DNAJC3 NM_006260.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC3	NM_006260.5	c.194-1110C>T		intron_variant	Intron 2 of 11	ENST00000602402.6	NP_006251.1
DNAJC3	XM_011521104.3	c.194-1110C>T		intron_variant	Intron 2 of 12		XP_011519406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC3	ENST00000602402.6	c.194-1110C>T		intron_variant	Intron 2 of 11	1	NM_006260.5	ENSP00000473631.1
DNAJC3	ENST00000376795.6	c.194-1110C>T		intron_variant	Intron 2 of 10	5		ENSP00000365991.6

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91308 AN: 151930 Hom.: 28575 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.581

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91409 AN: 152048 Hom.: 28618 Cov.: 32 AF XY: 0.603 AC XY: 44817 AN XY: 74312

African (AFR) AF: 0.790 AC: 32776 AN: 41510

American (AMR) AF: 0.566 AC: 8649 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3464

East Asian (EAS) AF: 0.644 AC: 3322 AN: 5162

South Asian (SAS) AF: 0.616 AC: 2969 AN: 4820

European-Finnish (FIN) AF: 0.525 AC: 5541 AN: 10554

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34046 AN: 67956

Other (OTH) AF: 0.584 AC: 1232 AN: 2110

Alfa AF: 0.527 Hom.: 59590

Bravo AF: 0.608

Asia WGS AF: 0.656 AC: 2282 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.80
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9302083; hg19: chr13-96374386;