10-72344966-C-A

Variant names:

• chr10-72344966-C-A
• rs146641977
• NM_017626.7:c.295G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017626.7(DNAJB12):​c.295G>T​(p.Val99Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V99I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJB12 NM_017626.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017626.7. 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
	DNAJB12	NM_017626.7	MANE Select	c.295G>T	p.Val99Phe	missense	Exon 2 of 9	NP_060096.4
	DNAJB12	NM_001365080.3		c.295G>T	p.Val99Phe	missense	Exon 2 of 9	NP_001352009.1	Q9NXW2-2
	DNAJB12	NM_001002762.5		c.295G>T	p.Val99Phe	missense	Exon 2 of 8	NP_001002762.3	Q9NXW2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB12	ENST00000444643.8	TSL:1 MANE Select	c.295G>T	p.Val99Phe	missense	Exon 2 of 9	ENSP00000403313.2	Q9NXW2-1
	DNAJB12	ENST00000394903.6	TSL:1	c.397G>T	p.Val133Phe	missense	Exon 2 of 9	ENSP00000378363.2	J3KPS0
	DNAJB12	ENST00000338820.7	TSL:2	c.397G>T	p.Val133Phe	missense	Exon 2 of 8	ENSP00000345575.3	J3KPS0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.81
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.10
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.038	D
Polyphen		0.89	P
Vest4		0.57
MVP		0.94
MPC		0.94
ClinPred		0.72	D
GERP RS		3.7
PromoterAI		-0.0070	Neutral
Varity_R		0.22
gMVP		0.47
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs146641977; hg19: chr10-74104724;