12-29443474-A-G

Position:

• chr12-29443474-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353179.2(OVCH1):​c.3149T>C​(p.Leu1050Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OVCH1 NM_001353179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

OVCH1 (HGNC:23080): (ovochymase 1) Predicted to enable metal ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OVCH1-AS1 (HGNC:44484): (OVCH1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12146473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCH1	NM_001353179.2	c.3149T>C	p.Leu1050Ser	missense_variant	25/26	ENST00000537054.2	NP_001340108.1
OVCH1-AS1	NR_073172.1	n.561-43412A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVCH1	ENST00000537054.2	c.3149T>C	p.Leu1050Ser	missense_variant	25/26	3	NM_001353179.2	ENSP00000445480	P1
OVCH1-AS1	ENST00000551108.2	n.561-43412A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 08, 2024

The c.3044T>C (p.L1015S) alteration is located in exon 25 (coding exon 25) of the OVCH1 gene. This alteration results from a T to C substitution at nucleotide position 3044, causing the leucine (L) at amino acid position 1015 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
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;D
REVEL	Benign	0.067
Sift	Benign	0.067	T;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.28
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.22
MPC		0.11
ClinPred		0.17	T
GERP RS		-1.5
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-29596407;