rs776875257

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172437.2(PEG10):​c.439C>A​(p.Pro147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. P147S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PEG10
NM_001172437.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58
Variant links:
Genes affected
PEG10 (HGNC:14005): (paternally expressed 10) This is a paternally expressed imprinted gene that is thought to have been derived from the Ty3/Gypsy family of retrotransposons. It contains two overlapping open reading frames, RF1 and RF2, and expresses two proteins: a shorter, gag-like protein (with a CCHC-type zinc finger domain) from RF1; and a longer, gag/pol-like fusion protein (with an additional aspartic protease motif) from RF1/RF2 by -1 translational frameshifting (-1 FS). While -1 FS has been observed in RNA viruses and transposons in both prokaryotes and eukaryotes, this gene represents the first example of -1 FS in a eukaryotic cellular gene. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC) and pseudoknot elements required for -1 FS. It is expressed in adult and embryonic tissues (most notably in placenta) and reported to have a role in cell proliferation, differentiation and apoptosis. Overexpression of this gene has been associated with several malignancies, such as hepatocellular carcinoma and B-cell lymphocytic leukemia. Knockout mice lacking this gene showed early embryonic lethality with placental defects, indicating the importance of this gene in embryonic development. Additional isoforms resulting from alternatively spliced transcript variants, and use of upstream non-AUG (CUG) start codon have been reported for this gene. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.049012363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEG10NM_001172437.2 linkc.439C>A p.Pro147Thr missense_variant Exon 2 of 2 NP_001165908.1 Q86TG7-4
PEG10NM_001184961.1 linkc.313C>A p.Pro105Thr missense_variant Exon 2 of 2 NP_001171890.1 Q86TG7
PEG10NM_015068.3 linkc.211C>A p.Pro71Thr missense_variant Exon 2 of 2 NP_055883.2 Q86TG7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEG10ENST00000612748.1 linkc.439C>A p.Pro147Thr missense_variant Exon 2 of 3 5 ENSP00000480676.1 A0A087WX23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000407
AC:
1
AN:
245732
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133466
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000293
Gnomad ASJ exome
AF:
0.00
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:
0.00000137
AC:
2
AN:
1460404
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
726398
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000827
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.4
DANN
Benign
0.28
DEOGEN2
Benign
0.035
.;T;.;T;T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.61
T;T;T;T;T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.049
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
N;.;.;.;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.4
N;.;.;.;.;.
REVEL
Benign
0.022
Sift
Benign
0.061
T;.;.;.;.;.
Sift4G
Benign
0.51
T;T;T;T;T;T
Polyphen
0.0
.;B;.;.;.;.
Vest4
0.21
MutPred
0.34
Gain of phosphorylation at P71 (P = 0.0227);.;.;Gain of phosphorylation at P71 (P = 0.0227);.;.;
MVP
0.043
MPC
0.86
ClinPred
0.017
T
GERP RS
-3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.28

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.

Other links and lift over

dbSNP: rs776875257; hg19: chr7-94293079; API