rs2659690

Variant names:

• chr3-128462934-A-G
• rs2659690
• NM_153330.6:c.312T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153330.6(DNAJB8):​c.312T>C​(p.Phe104Phe) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAJB8	NM_153330.6	c.312T>C	p.Phe104Phe	synonymous_variant	Exon 3 of 3	ENST00000319153.4	NP_699161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB8	ENST00000319153.4	c.312T>C	p.Phe104Phe	synonymous_variant	Exon 3 of 3	1	NM_153330.6	ENSP00000316053.3
DNAJB8	ENST00000469083.1	c.312T>C	p.Phe104Phe	synonymous_variant	Exon 2 of 2	2		ENSP00000417418.1

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

GnomAD2 exomes AF: 0.557 AC: 139727 AN: 250768 AF XY: 0.561

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 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

African (AFR) AF: 0.403 AC: 13475 AN: 33478

American (AMR) AF: 0.464 AC: 20755 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15079 AN: 26136

East Asian (EAS) AF: 0.341 AC: 13555 AN: 39700

South Asian (SAS) AF: 0.457 AC: 39423 AN: 86258

European-Finnish (FIN) AF: 0.757 AC: 40453 AN: 53412

Middle Eastern (MID) AF: 0.477 AC: 2753 AN: 5768

European-Non Finnish (NFE) AF: 0.636 AC: 707320 AN: 1112004

Other (OTH) AF: 0.584 AC: 35243 AN: 60396

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

African (AFR) AF: 0.419 AC: 17365 AN: 41456

American (AMR) AF: 0.522 AC: 7985 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3472

East Asian (EAS) AF: 0.364 AC: 1871 AN: 5140

South Asian (SAS) AF: 0.438 AC: 2106 AN: 4806

European-Finnish (FIN) AF: 0.781 AC: 8265 AN: 10582

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42710 AN: 67954

Other (OTH) AF: 0.553 AC: 1170 AN: 2114

Alfa AF: 0.603 Hom.: 33337

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
PhyloP100		-0.14
Mutation Taster		=99/1	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: rs2659690; hg19: chr3-128181777; COSMIC: COSV59878178; COSMIC: COSV59878178;