Variant 7-108573088-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012328.3(DNAJB9):c.407G>A(p.Arg136His) variant causes a missense change. The variant allele was found at a frequency of 0.00498 in 1,614,058 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.026 ( 171 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 155 hom. )

Consequence

DNAJB9
NM_012328.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

DNAJB9 (HGNC:6968): (DnaJ heat shock protein family (Hsp40) member B9) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. This gene is a member of the type 2 subgroup of DnaJ proteins. The encoded protein is localized to the endoplasmic reticulum. This protein is induced by endoplasmic reticulum stress and plays a role in protecting stressed cells from apoptosis. [provided by RefSeq, Dec 2010]

DNAJB9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011062026).

BP6

Variant 7-108573088-G-A is Benign according to our data. Variant chr7-108573088-G-A is described in ClinVar as [Benign]. Clinvar id is 780704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB9	NM_012328.3 linkuse as main transcript	c.407G>A	p.Arg136His	missense_variant	3/3	ENST00000249356.4	NP_036460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB9	ENST00000249356.4 linkuse as main transcript	c.407G>A	p.Arg136His	missense_variant	3/3	1	NM_012328.3	ENSP00000249356	P1
DNAJB9	ENST00000465725.1 linkuse as main transcript	n.229+1145G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3880

AN:

152152

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0879

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00709

AC:

1782

AN:

251300

Hom.:

AF XY:

0.00509

AC XY:

692

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0928

Gnomad AMR exome

AF:

0.00529

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000554

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00284

AC:

4155

AN:

1461788

Hom.:

155

Cov.:

AF XY:

0.00246

AC XY:

1790

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.00637

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.0255

AC:

3888

AN:

152270

Hom.:

171

Cov.:

AF XY:

0.0244

AC XY:

1816

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00574

Hom.:

Bravo

AF:

0.0293

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0892

AC:

393

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00854

AC:

1037

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

2.3

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MVP

0.57

MPC

0.011

ClinPred

0.0057

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.19

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