Genetic Variant NM_001080507.3:c.71T>C (chr6-73369722-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080507.3(OOEP):c.71T>C(p.Leu24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L24R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

OOEP
NM_001080507.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320

Publications

0 publications found

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:

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

OOEP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080507.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OOEP	NM_001080507.3	MANE Select	c.71T>C	p.Leu24Pro	missense	Exon 1 of 3	NP_001073976.1	A6NGQ2
OOEP	NM_001428256.1		c.26-337T>C		intron	N/A	NP_001415185.1	F2Z364
OOEP-AS1	NR_174946.1		n.19A>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OOEP	ENST00000370359.6	TSL:1 MANE Select	c.71T>C	p.Leu24Pro	missense	Exon 1 of 3	ENSP00000359384.5	A6NGQ2
OOEP	ENST00000370363.5	TSL:1	c.26-337T>C		intron	N/A	ENSP00000359388.1	F2Z364
OOEP	ENST00000441145.1	TSL:3	c.26-337T>C		intron	N/A	ENSP00000397430.1	C9J915

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111866

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.31

M_CAP

Benign

0.0034

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.32

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.40

REVEL

Benign

0.14

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.51

MutPred

0.39

Gain of loop (P = 0.002)

MVP

0.26

MPC

1.3

ClinPred

0.33

GERP RS

0.78

PromoterAI

0.11

Neutral

(source)

Varity_R

0.10

gMVP

0.29

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over