6-73369771-C-T

Position:

• chr6-73369771-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080507.3(OOEP):​c.22G>A​(p.Ala8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: OOEP NM_001080507.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.313

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]

OOEP-AS1 (HGNC:39192): (OOEP antisense RNA 1)

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=0.03554544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OOEP	NM_001080507.3	c.22G>A	p.Ala8Thr	missense_variant	1/3	ENST00000370359.6
OOEP-AS1	NR_174946.1	n.68C>T		non_coding_transcript_exon_variant	1/2
OOEP	XM_047418829.1	c.22G>A	p.Ala8Thr	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OOEP	ENST00000370359.6	c.22G>A	p.Ala8Thr	missense_variant	1/3	1	NM_001080507.3	P1
OOEP	ENST00000370363.5	c.26-386G>A		intron_variant		1
OOEP-AS1	ENST00000445350.2	n.68C>T		non_coding_transcript_exon_variant	1/2	3
OOEP	ENST00000441145.1	c.26-386G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 36 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000318 AC: 79 AN: 248374 Hom.: 0 AF XY: 0.000297 AC XY: 40 AN XY: 134818

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000471

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000339 AC: 496 AN: 1461274 Hom.: 0 Cov.: 31 AF XY: 0.000348 AC XY: 253 AN XY: 726922

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000565

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74498

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000465 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000469 AC: 4

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000763

EpiControl AF: 0.00113

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

Sep 01, 2021

The c.22G>A (p.A8T) alteration is located in exon 1 (coding exon 1) of the OOEP gene. This alteration results from a G to A substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 to be replaced by a threonine (T). 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	0.092
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.89
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.091
Sift	Benign	0.57	T
Sift4G	Benign	0.65	T
Polyphen		0.94	P
Vest4		0.10
MVP		0.14
MPC		0.29
ClinPred		0.013	T
GERP RS		0.87
Varity_R		0.038
gMVP		0.16

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: rs202009078; hg19: chr6-74079494; COSMIC: COSV100949778; COSMIC: COSV100949778;