6-73369731-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080507.3(OOEP):ā€‹c.62T>Cā€‹(p.Leu21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,684 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

OOEP
NM_001080507.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.857
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-AS1 (HGNC:39192): (OOEP antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1369912).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OOEPNM_001080507.3 linkuse as main transcriptc.62T>C p.Leu21Pro missense_variant 1/3 ENST00000370359.6
OOEP-AS1NR_174946.1 linkuse as main transcriptn.28A>G non_coding_transcript_exon_variant 1/2
OOEPXM_047418829.1 linkuse as main transcriptc.62T>C p.Leu21Pro missense_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OOEPENST00000370359.6 linkuse as main transcriptc.62T>C p.Leu21Pro missense_variant 1/31 NM_001080507.3 P1
OOEPENST00000370363.5 linkuse as main transcriptc.26-346T>C intron_variant 1
OOEP-AS1ENST00000445350.2 linkuse as main transcriptn.28A>G non_coding_transcript_exon_variant 1/23
OOEPENST00000441145.1 linkuse as main transcriptc.26-346T>C intron_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
249186
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135212
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461684
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJun 01, 2023The c.62T>C (p.L21P) alteration is located in exon 1 (coding exon 1) of the OOEP gene. This alteration results from a T to C substitution at nucleotide position 62, causing the leucine (L) at amino acid position 21 to be replaced by a proline (P). 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
0.066
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.96
DANN
Benign
0.78
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.85
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.23
N
REVEL
Benign
0.085
Sift
Benign
0.16
T
Sift4G
Benign
0.18
T
Polyphen
0.99
D
Vest4
0.20
MutPred
0.36
Gain of loop (P = 3e-04);
MVP
0.19
MPC
0.54
ClinPred
0.18
T
GERP RS
0.43
Varity_R
0.084
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1321542843; hg19: chr6-74079454; API