Variant 6-73369322-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001080507.3(OOEP):c.254T>G(p.Ile85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,613,638 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 0.00042 ( 2 hom. )

Consequence

OOEP
NM_001080507.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.237

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029318273).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OOEP	NM_001080507.3 linkuse as main transcript	c.254T>G	p.Ile85Arg	missense_variant	2/3	ENST00000370359.6	NP_001073976.1
OOEP	XM_047418829.1 linkuse as main transcript	c.137T>G	p.Ile46Arg	missense_variant	2/3		XP_047274785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OOEP	ENST00000370359.6 linkuse as main transcript	c.254T>G	p.Ile85Arg	missense_variant	2/3	1	NM_001080507.3	ENSP00000359384	P1
OOEP	ENST00000370363.5 linkuse as main transcript	c.89T>G	p.Ile30Arg	missense_variant	3/4	1		ENSP00000359388
OOEP	ENST00000441145.1 linkuse as main transcript	c.89T>G	p.Ile30Arg	missense_variant	2/2	3		ENSP00000397430

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000253

AC:

AN:

249124

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

135150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000460

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000422

AC:

617

AN:

1461642

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

304

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000518

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000237

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000363

AC:

ExAC

AF:

0.000265

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.254T>G (p.I85R) alteration is located in exon 2 (coding exon 2) of the OOEP gene. This alteration results from a T to G substitution at nucleotide position 254, causing the isoleucine (I) at amino acid position 85 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.4

DANN

Benign

0.60

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.39

T;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.095

.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.029

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.14

B;B;.

Vest4

0.35

MVP

0.12

MPC

0.52

ClinPred

0.023

GERP RS

-5.0

Varity_R

0.11

gMVP

0.063

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over