Variant 9-34990747-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001349723.3(DNAJB5):c.117G>T(p.Met39Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000307 in 1,399,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DNAJB5
NM_001349723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

DNAJB5 (HGNC:14887): (DnaJ heat shock protein family (Hsp40) member B5) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins. The encoded protein contains an N-terminal DNAJ domain and a C-terminal substrate binding domain but lacks the cysteine-rich domain found in other DNAJ family members. In mice, a multi-protein complex containing this protein, thioredoxin 1, and histone deacetylase 4, serves as a master negative regulator of cardiac hypertrophy. [provided by RefSeq, Mar 2017]

DNAJB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26886505).

BS2

High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB5	NM_001349723.3 linkuse as main transcript	c.117G>T	p.Met39Ile	missense_variant	2/5	ENST00000682809.1	NP_001336652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB5	ENST00000682809.1 linkuse as main transcript	c.117G>T	p.Met39Ile	missense_variant	2/5		NM_001349723.3	ENSP00000507741		O75953-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

152432

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000344

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000307

AC:

AN:

1399410

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

690214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000399

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Oct 26, 2022

The c.243G>T (p.M81I) alteration is located in exon 2 (coding exon 2) of the DNAJB5 gene. This alteration results from a G to T substitution at nucleotide position 243, causing the methionine (M) at amino acid position 81 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

-0.0050

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.53

MutPred

0.34

Gain of catalytic residue at L86 (P = 0.0639);.;

MVP

0.54

MPC

1.4

ClinPred

0.97

GERP RS

4.6

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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