Variant chr8-66076802-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033105.6(DNAJC5B):c.262C>G(p.Leu88Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DNAJC5B
NM_033105.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

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]

DNAJC5B links:

DNAJC5B (HGNC:):

DNAJC5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5B	NM_033105.6 linkuse as main transcript	c.262C>G	p.Leu88Val	missense_variant	4/6	ENST00000276570.10	NP_149096.2	Q9UF47A0A024R7Z1
DNAJC5B	NM_001349432.2 linkuse as main transcript	c.262C>G	p.Leu88Val	missense_variant	4/6		NP_001336361.1
DNAJC5B	XM_011517620.3 linkuse as main transcript	c.262C>G	p.Leu88Val	missense_variant	4/6		XP_011515922.1
DNAJC5B	NR_146171.2 linkuse as main transcript	n.2100C>G		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC5B	ENST00000276570.10 linkuse as main transcript	c.262C>G	p.Leu88Val	missense_variant	4/6	1	NM_033105.6	ENSP00000276570.5	Q9UF47
DNAJC5B	ENST00000519330.1 linkuse as main transcript	n.2039C>G		non_coding_transcript_exon_variant	5/7	1
DNAJC5B	ENST00000522619.1 linkuse as main transcript	c.262C>G	p.Leu88Val	missense_variant	3/3	3		ENSP00000430196.1	E5RGF4
DNAJC5B	ENST00000524076.5 linkuse as main transcript	n.413C>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251430

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000144

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2023

The c.262C>G (p.L88V) alteration is located in exon 4 (coding exon 2) of the DNAJC5B gene. This alteration results from a C to G substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

3.3

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.62

Sift

Benign

0.033

D;T

Sift4G

Uncertain

0.019

D;T

Polyphen

1.0

D;.

Vest4

0.71

MVP

0.86

MPC

0.67

ClinPred

0.78

GERP RS

5.7

Varity_R

0.36

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over