Variant 10-72340809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_017626.7(DNAJB12):c.703C>T(p.Arg235Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DNAJB12
NM_017626.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.35

Variant links:

Genes affected

DNAJB12 (HGNC:14891): (DnaJ heat shock protein family (Hsp40) member B12) DNAJB12 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

DNAJB12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB12	NM_017626.7 link	c.703C>T	p.Arg235Cys	missense_variant	5/9	ENST00000444643.8	NP_060096.4	Q9NXW2-1J3KPS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB12	ENST00000444643.8 link	c.703C>T	p.Arg235Cys	missense_variant	5/9	1	NM_017626.7	ENSP00000403313.2		Q9NXW2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727174

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2023

The c.805C>T (p.R269C) alteration is located in exon 5 (coding exon 5) of the DNAJB12 gene. This alteration results from a C to T substitution at nucleotide position 805, causing the arginine (R) at amino acid position 269 to be replaced by a cysteine (C). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;T;T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Uncertain

0.058

MutationAssessor

Pathogenic

3.5

.;.;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.4

D;D;D;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0030

D;D;D;.

Sift4G

Uncertain

0.011

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.83

MutPred

0.48

.;.;Gain of sheet (P = 4e-04);.;

MVP

0.91

MPC

1.3

ClinPred

1.0

GERP RS

5.7

Varity_R

0.40

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over