1-111414716-C-G

Position:

• chr1-111414716-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.1785G>C​(p.Glu595Asp) 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. E595Q) 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: -0.360

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=0.07603088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVGP1	NM_002557.4	c.1785G>C	p.Glu595Asp	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.1785G>C	p.Glu595Asp	missense_variant	11/11	1	NM_002557.4	ENSP00000358747.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

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

May 17, 2023

The c.1785G>C (p.E595D) 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 1785, causing the glutamic acid (E) at amino acid position 595 to be replaced by an aspartic acid (D). 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	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.024
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.070		Loss of methylation at R593 (P = 0.1645);
MVP		0.27
MPC		0.22
ClinPred		0.21	T
GERP RS		-2.2
Varity_R		0.19
gMVP		0.11

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: chr1-111957338;