8-66021385-G-A

Variant names:

• chr8-66021385-G-A
• rs953177
• ENST00000837914.1:n.61C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000837914.1(ENSG00000309029):​n.61C>T variant causes a non coding transcript exon 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: ENSG00000309029 ENST00000837914.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 4 publications found

Genes affected

ENSG00000309029 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000837914.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5B	NM_001349432.2		c.-142+6321G>A		intron	N/A	NP_001336361.1
	DNAJC5B	NM_033105.6	MANE Select	c.-462G>A		upstream_gene	N/A	NP_149096.2
	DNAJC5B	NR_146171.2		n.-168G>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000309029	ENST00000837914.1		n.61C>T		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000309029	ENST00000837915.1		n.26-152C>T		intron	N/A
	DNAJC5B	ENST00000276570.10	TSL:1 MANE Select	c.-462G>A		upstream_gene	N/A	ENSP00000276570.5

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

African (AFR) AF: 0.482 AC: 19986 AN: 41454

American (AMR) AF: 0.104 AC: 1595 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5184

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4826

European-Finnish (FIN) AF: 0.0487 AC: 517 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0606 AC: 4120 AN: 68012

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.102 Hom.: 2315

Bravo AF: 0.197

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-0.42
PromoterAI		0.0066	Neutral

Splicing

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

Other links and lift over

dbSNP: rs953177; hg19: chr8-66933620;