12-29433785-C-T

Variant names:

• chr12-29433785-C-T
• rs1017001580
• ENST00000318184.9:c.3293G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000318184.9(OVCH1):​c.3293G>A​(p.Arg1098Lys) 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. 16/19 in silico tools predict a benign outcome for this variant. 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. R1098T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OVCH1 ENST00000318184.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051689804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000318184.9. 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
	OVCH1-AS1	NR_073170.1		n.561-27949C>T		intron	N/A
	OVCH1-AS1	NR_073171.1		n.561-28011C>T		intron	N/A
	OVCH1-AS1	NR_073172.1		n.560+43932C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVCH1	ENST00000318184.9	TSL:1	c.3293G>A	p.Arg1098Lys	missense	Exon 27 of 28	ENSP00000326708.5	Q7RTY7-1
	OVCH1	ENST00000539117.5	TSL:3	n.262+9576G>A		intron	N/A	ENSP00000445260.1	H0YGY6
	OVCH1-AS1	ENST00000549411.1	TSL:3	n.140+7721C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1267590 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 620844

African (AFR) AF: 0.00 AC: 0 AN: 26792

American (AMR) AF: 0.00 AC: 0 AN: 28354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23052

East Asian (EAS) AF: 0.00 AC: 0 AN: 31792

South Asian (SAS) AF: 0.00 AC: 0 AN: 70532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 987912

Other (OTH) AF: 0.00 AC: 0 AN: 52010

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.44
DANN	Benign	0.45
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0035	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.77	T
PhyloP100		-0.19
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.15
MutPred		0.24		Gain of methylation at R1098 (P = 0.0126)
MVP		0.40
MPC		0.033
ClinPred		0.069	T
GERP RS		-0.41
gMVP		0.019
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1017001580; hg19: chr12-29586718;