10-67797171-C-G

Variant names:

• chr10-67797171-C-G
• NM_021800.3:c.542G>C

Variant summary

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

The NM_021800.3(DNAJC12):​c.542G>C​(p.Trp181Ser) 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: DNAJC12 NM_021800.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

Genes affected

DNAJC12 (HGNC:28908): (DnaJ heat shock protein family (Hsp40) member C12) This gene encodes a member of a subclass of the HSP40/DnaJ protein family. Members of this family of proteins are associated with complex assembly, protein folding, and export. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
DNAJC12	NM_021800.3	c.542G>C	p.Trp181Ser	missense_variant	Exon 5 of 5	ENST00000225171.7	NP_068572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC12	ENST00000225171.7	c.542G>C	p.Trp181Ser	missense_variant	Exon 5 of 5	1	NM_021800.3	ENSP00000225171.2
DNAJC12	ENST00000483798.6	c.632G>C	p.Trp211Ser	missense_variant	Exon 6 of 6	3		ENSP00000474215.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542G>C (p.W181S) alteration is located in exon 5 (coding exon 5) of the DNAJC12 gene. This alteration results from a G to C substitution at nucleotide position 542, causing the tryptophan (W) at amino acid position 181 to be replaced by a serine (S). 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	0.54
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-8.8	D;.
REVEL	Benign	0.26
Sift	Uncertain	0.016	D;.
Sift4G	Uncertain	0.019	D;D
Polyphen		0.99	D;.
Vest4		0.75
MutPred		0.57		Gain of disorder (P = 0.0014);.;
MVP		0.48
MPC		0.47
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.76
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-69556929;