rs953177

Variant names:

• chr8-66021385-G-A
• rs953177
• NM_001349432.2:c.-142+6321G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349432.2(DNAJC5B):​c.-142+6321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,178 control chromosomes in the GnomAD database, including 5,213 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 0.18 (5213 hom., cov: 32)
• Consequence: DNAJC5B NM_001349432.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

Genes affected

DNAJC5B (HGNC:24138): (DnaJ heat shock protein family (Hsp40) member C5 beta) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins that is characterized by an N-terminal DNAJ domain, a linker region, and a cysteine-rich C-terminal domain. The encoded protein, together with heat shock protein 70, is thought to regulate the proper folding of other proteins. The orthologous mouse protein is membrane-associated and is targeted to the trans-golgi network. [provided by RefSeq, Mar 2017]

LOC105375883 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5B	NM_033105.6	c.-462G>A		upstream_gene_variant		ENST00000276570.10	NP_149096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC5B	ENST00000276570.10	c.-462G>A		upstream_gene_variant		1	NM_033105.6	ENSP00000276570.5
DNAJC5B	ENST00000519330.1	n.-229G>A		upstream_gene_variant		1
DNAJC5B	ENST00000524076.5	n.-175G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27221 AN: 152060 Hom.: 5205 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.179 AC: 27273 AN: 152178 Hom.: 5213 Cov.: 32 AF XY: 0.174 AC XY: 12934 AN XY: 74424

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0487

Gnomad4 NFE AF: 0.0606

Gnomad4 OTH AF: 0.150

Alfa AF: 0.0843 Hom.: 1103

Bravo AF: 0.197

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs953177; hg19: chr8-66933620;