6-73369251-T-C

Position:

• chr6-73369251-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001080507.3(OOEP):​c.325A>G​(p.Met109Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OOEP NM_001080507.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349

Genes affected

OOEP (HGNC:21382): (oocyte expressed protein) Predicted to enable RNA binding activity. Predicted to be involved in several processes, including cytoskeleton organization; positive regulation of double-strand break repair via homologous recombination; and positive regulation of meiotic nuclear division. Predicted to act upstream of or within several processes, including embryo implantation; in utero embryonic development; and protein phosphorylation. Located in cytoplasm and nucleus. Part of subcortical maternal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08728638).
• BP6: Variant 6-73369251-T-C is Benign according to our data. Variant chr6-73369251-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3204342.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OOEP	NM_001080507.3	c.325A>G	p.Met109Val	missense_variant	2/3	ENST00000370359.6
OOEP	XM_047418829.1	c.208A>G	p.Met70Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OOEP	ENST00000370359.6	c.325A>G	p.Met109Val	missense_variant	2/3	1	NM_001080507.3	P1
OOEP	ENST00000370363.5	c.160A>G	p.Met54Val	missense_variant	3/4	1
OOEP	ENST00000441145.1	c.160A>G	p.Met54Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.86
DANN	Benign	0.58
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.051
Sift	Benign	0.84	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.070
MutPred		0.58		.;Loss of catalytic residue at M109 (P = 0.0091);.;
MVP		0.15
MPC		0.30
ClinPred		0.060	T
GERP RS		1.9
Varity_R		0.049
gMVP		0.10

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: rs1769004525; hg19: chr6-74078974;