rs3962158

chr19-14518338-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006145.3(DNAJB1):c.12C>T(p.Asp4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,584,304 control chromosomes in the GnomAD database, including 85,744 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 0.35 (9468 hom., cov: 34)
  • Exomes 𝑓: 0.32 (76276 hom.)
• Consequence: DNAJB1 NM_006145.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

Genes affected

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

TECR (HGNC:4551): (trans-2,3-enoyl-CoA reductase) This gene encodes a multi-pass membrane protein that resides in the endoplasmic reticulum, and belongs to the steroid 5-alpha reductase family. The elongation of microsomal long and very long chain fatty acid consists of 4 sequential reactions. This protein catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.168 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB1	NM_006145.3	c.12C>T	p.Asp4=	synonymous_variant	1/3	ENST00000254322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB1	ENST00000254322.3	c.12C>T	p.Asp4=	synonymous_variant	1/3	1	NM_006145.3	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52404 AN: 151942 Hom.: 9442 Cov.: 34

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.323

GnomAD3 exomes AF: 0.341 AC: 74785 AN: 219030 Hom.: 13357 AF XY: 0.342 AC XY: 41324 AN XY: 120710

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.0908

Gnomad SAS exome AF: 0.440

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.321 AC: 460227 AN: 1432244 Hom.: 76276 Cov.: 37 AF XY: 0.324 AC XY: 231003 AN XY: 712738

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.0845

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.345 AC: 52475 AN: 152060 Hom.: 9468 Cov.: 34 AF XY: 0.348 AC XY: 25900 AN XY: 74352

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.320

Alfa AF: 0.325 Hom.: 1727

Bravo AF: 0.342

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	7.7
Dann	Benign	0.96
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs3962158; hg19: chr19-14629150; COSMIC: COSV54316981; COSMIC: COSV54316981;