rs10067

Positions:

• chr1-111414689-G-C
• chr1-111414689-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002557.4(OVGP1):​c.1812C>G​(p.His604Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,860 control chromosomes in the GnomAD database, including 17,924 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (4322 hom., cov: 32)
  • Exomes 𝑓: 0.11 (13602 hom.)
• Consequence: OVGP1 NM_002557.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

Genes affected

OVGP1 (HGNC:8524): (oviductal glycoprotein 1) This gene encodes a large, carbohydrate-rich, epithelial glycoprotein with numerous O-glycosylation sites located within threonine, serine, and proline-rich tandem repeats. The gene is similar to members of the mucin and the glycosyl hydrolase 18 gene families. Regulation of expression may be estrogen-dependent. Gene expression and protein secretion occur during late follicular development through early cleavage-stage embryonic development. The protein is secreted from non-ciliated oviductal epithelial cells and associates with ovulated oocytes, blastomeres, and spermatozoan acrosomal regions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015249252).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVGP1	NM_002557.4	c.1812C>G	p.His604Gln	missense_variant	11/11	ENST00000369732.4	NP_002548.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVGP1	ENST00000369732.4	c.1812C>G	p.His604Gln	missense_variant	11/11	1	NM_002557.4	ENSP00000358747.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29450 AN: 151992 Hom.: 4313 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0826

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.161 AC: 40335 AN: 251146 Hom.: 4692 AF XY: 0.157 AC XY: 21242 AN XY: 135732

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0889

Gnomad EAS exome AF: 0.403

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.0833

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.109 AC: 159234 AN: 1461750 Hom.: 13602 Cov.: 39 AF XY: 0.111 AC XY: 80677 AN XY: 727174

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.0893

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.194 AC: 29506 AN: 152110 Hom.: 4322 Cov.: 32 AF XY: 0.197 AC XY: 14655 AN XY: 74328

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0894

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.184

Alfa AF: 0.104 Hom.: 980

Bravo AF: 0.205

TwinsUK AF: 0.0758 AC: 281

ALSPAC AF: 0.0771 AC: 297

ESP6500AA AF: 0.386 AC: 1700

ESP6500EA AF: 0.0824 AC: 709

ExAC AF: 0.165 AC: 20004

Asia WGS AF: 0.298 AC: 1036 AN: 3478

EpiCase AF: 0.0879

EpiControl AF: 0.0956

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.64
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.082
Sift	Benign	0.13	T
Sift4G	Benign	0.43	T
Polyphen		0.0050	B
Vest4		0.034
MutPred		0.051		Loss of catalytic residue at H604 (P = 0.0985);
MPC		0.089
ClinPred		0.0049	T
GERP RS		0.21
Varity_R		0.13
gMVP		0.045

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: rs10067; hg19: chr1-111957311; COSMIC: COSV63857932; COSMIC: COSV63857932;