10-72354899-G-A

Position:

• chr10-72354899-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000394903.6(DNAJB12):​c.101C>T​(p.Ala34Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAJB12 ENST00000394903.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB12	NM_017626.7	c.-2C>T		5_prime_UTR_variant	1/9	ENST00000444643.8	NP_060096.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB12	ENST00000394903.6	c.101C>T	p.Ala34Val	missense_variant	1/9	1		ENSP00000378363.2
DNAJB12	ENST00000444643.8	c.-2C>T		5_prime_UTR_variant	1/9	1	NM_017626.7	ENSP00000403313.2
DNAJB12	ENST00000338820.7	c.101C>T	p.Ala34Val	missense_variant	1/8	2		ENSP00000345575.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2022

The c.101C>T (p.A34V) alteration is located in exon 1 (coding exon 1) of the DNAJB12 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a valine (V). 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	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0064	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.055
Sift	Benign	0.048	D;D
Sift4G	Uncertain	0.058	T;T
Vest4		0.61
MVP		0.54
MPC		1.1
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.23

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

Other links and lift over

dbSNP: rs375290343; hg19: chr10-74114657;