Variant 3-128462789-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153330.6(DNAJB8):c.457A>C(p.Met153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,613,828 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 105 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 97 hom. )

Consequence

DNAJB8
NM_153330.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.03

Variant links:

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]

DNAJB8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018289387).

BP6

Variant 3-128462789-T-G is Benign according to our data. Variant chr3-128462789-T-G is described in ClinVar as [Benign]. Clinvar id is 791952.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB8	NM_153330.6 linkuse as main transcript	c.457A>C	p.Met153Leu	missense_variant	3/3	ENST00000319153.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB8	ENST00000319153.4 linkuse as main transcript	c.457A>C	p.Met153Leu	missense_variant	3/3	1	NM_153330.6	P1
DNAJB8	ENST00000469083.1 linkuse as main transcript	c.457A>C	p.Met153Leu	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2984

AN:

151872

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00508

AC:

1276

AN:

251140

Hom.:

AF XY:

0.00353

AC XY:

480

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0697

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00210

AC:

3067

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1268

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0719

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.00452

GnomAD4 genome

AF:

0.0197

AC:

2990

AN:

151990

Hom.:

105

Cov.:

AF XY:

0.0192

AC XY:

1425

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0680

Gnomad4 AMR

AF:

0.00798

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.0227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0626

AC:

276

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00636

AC:

772

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.0050

Dann

Benign

0.56

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.047

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.0090

Sift

Benign

0.23

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.085

MutPred

0.13

Loss of glycosylation at S157 (P = 0.0637);Loss of glycosylation at S157 (P = 0.0637);

MVP

0.10

MPC

0.098

ClinPred

0.0066

GERP RS

-5.0

Varity_R

0.084

gMVP

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

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