rs2659690

chr3-128462934-A-G

Variant summary

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

The NM_153330.6(DNAJB8):c.312T>C(p.Phe104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,613,890 control chromosomes in the GnomAD database, including 299,194 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 0.55 (24307 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274887 hom.)
• Consequence: DNAJB8 NM_153330.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

Genes affected

DNAJB8 (HGNC:23699): (DnaJ heat shock protein family (Hsp40) member B8) The protein encoded by this gene belongs to the DNAJ/HSP40 family of proteins that regulate chaperone activity. This family member suppresses aggregation and toxicity of polyglutamine proteins, and the C-terminal tail is essential for this activity. It has been implicated as a cancer-testis antigen and as a cancer stem-like cell antigen involved in renal cell carcinoma. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB8	NM_153330.6	c.312T>C	p.Phe104=	synonymous_variant	3/3	ENST00000319153.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB8	ENST00000319153.4	c.312T>C	p.Phe104=	synonymous_variant	3/3	1	NM_153330.6	P1
DNAJB8	ENST00000469083.1	c.312T>C	p.Phe104=	synonymous_variant	2/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84116 AN: 151900 Hom.: 24304 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.558

GnomAD3 exomes AF: 0.557 AC: 139727 AN: 250768 Hom.: 40779 AF XY: 0.561 AC XY: 76103 AN XY: 135604

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.587

Gnomad EAS exome AF: 0.351

Gnomad SAS exome AF: 0.462

Gnomad FIN exome AF: 0.764

Gnomad NFE exome AF: 0.627

Gnomad OTH exome AF: 0.562

GnomAD4 exome AF: 0.607 AC: 888056 AN: 1461872 Hom.: 274887 Cov.: 82 AF XY: 0.604 AC XY: 438935 AN XY: 727236

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.554 AC: 84159 AN: 152018 Hom.: 24307 Cov.: 32 AF XY: 0.555 AC XY: 41253 AN XY: 74336

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.553

Alfa AF: 0.599 Hom.: 26256

Bravo AF: 0.529

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.32
Dann	Benign	0.35

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: rs2659690; hg19: chr3-128181777; COSMIC: COSV59878178; COSMIC: COSV59878178;