1-111414718-C-G

Position:

• chr1-111414718-C-G

Variant summary

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

The NM_002557.4(OVGP1):​c.1783G>C​(p.Glu595Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E595D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OVGP1 NM_002557.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00

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 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=0.07594052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVGP1	NM_002557.4	c.1783G>C	p.Glu595Gln	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.1783G>C	p.Glu595Gln	missense_variant	11/11	1	NM_002557.4	ENSP00000358747.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Dec 11, 2023

The c.1783G>C (p.E595Q) alteration is located in exon 11 (coding exon 11) of the OVGP1 gene. This alteration results from a G to C substitution at nucleotide position 1783, causing the glutamic acid (E) at amino acid position 595 to be replaced by a glutamine (Q). 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	Benign	0.089
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.030
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Polyphen		0.062	B
Vest4		0.16
MutPred		0.097		Gain of MoRF binding (P = 0.0509);
MVP		0.31
MPC		0.28
ClinPred		0.22	T
GERP RS		0.22
Varity_R		0.22
gMVP		0.17

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: rs767264544; hg19: chr1-111957340;