Genetic Variant DNAJB9:p.Thr88Arg (chr7-108572944-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012328.3(DNAJB9):c.263C>G(p.Thr88Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

DNAJB9
NM_012328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14087495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012328.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB9	NM_012328.3	MANE Select	c.263C>G	p.Thr88Arg	missense	Exon 3 of 3	NP_036460.1	Q6FIF1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJB9	ENST00000249356.4	TSL:1 MANE Select	c.263C>G	p.Thr88Arg	missense	Exon 3 of 3	ENSP00000249356.3	Q9UBS3
DNAJB9	ENST00000860473.1		c.263C>G	p.Thr88Arg	missense	Exon 3 of 3	ENSP00000530532.1
DNAJB9	ENST00000860474.1		c.263C>G	p.Thr88Arg	missense	Exon 2 of 2	ENSP00000530533.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251224

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111864

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.029

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

PhyloP100

4.3

PrimateAI

Benign

0.45

PROVEAN

Benign

0.89

REVEL

Benign

0.089

Sift

Benign

0.55

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.19

MutPred

0.25

Gain of MoRF binding (P = 0.0251)

MVP

0.74

MPC

0.011

ClinPred

0.24

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over