8-66062017-T-C

Position:

• chr8-66062017-T-C

Variant summary

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

The ENST00000276570.10(DNAJC5B):​c.119+10351T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,082 control chromosomes in the GnomAD database, including 11,751 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 0.32 (11751 hom., cov: 32)
• Consequence: DNAJC5B ENST00000276570.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5B	NM_033105.6	c.119+10351T>C		intron_variant		ENST00000276570.10	NP_149096.2
DNAJC5B	NM_001349432.2	c.119+10351T>C		intron_variant			NP_001336361.1
DNAJC5B	XM_011517620.3	c.119+10351T>C		intron_variant			XP_011515922.1
DNAJC5B	NR_146171.2	n.1957+4008T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5B	ENST00000276570.10	c.119+10351T>C		intron_variant		1	NM_033105.6	ENSP00000276570	P1
DNAJC5B	ENST00000519330.1	n.1896+4008T>C		intron_variant, non_coding_transcript_variant		1
DNAJC5B	ENST00000522619.1	c.119+10351T>C		intron_variant		3		ENSP00000430196
DNAJC5B	ENST00000524076.5	n.271-14643T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48781 AN: 151962 Hom.: 11704 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.321 AC: 48883 AN: 152082 Hom.: 11751 Cov.: 32 AF XY: 0.319 AC XY: 23692 AN XY: 74344

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.288

Alfa AF: 0.166 Hom.: 3941

Bravo AF: 0.350

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.73
DANN	Benign	0.52

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: rs13279522; hg19: chr8-66974252;