Genetic Variant ENST00000612748.1:c.39G>T (chr7-94663367-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000612748.1(PEG10):c.39G>T(p.Arg13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,274,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

PEG10
ENST00000612748.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.563

Publications

0 publications found

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]

PEG10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106003106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PEG10	NM_001172437.2 link	c.39G>T	p.Arg13Ser	missense_variant	Exon 2 of 2	NP_001165908.1	Q86TG7-4
PEG10	NM_001172438.3 link	c.39G>T	p.Arg13Ser	missense_variant	Exon 2 of 2	NP_001165909.1	Q86TG7-5
PEG10	NM_001184961.1 link	c.-88G>T		5_prime_UTR_variant	Exon 2 of 2	NP_001171890.1	Q86TG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEG10	ENST00000612748.1 link	c.39G>T	p.Arg13Ser	missense_variant	Exon 2 of 3	5		ENSP00000480676.1		A0A087WX23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.85e-7

AC:

AN:

1274180

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

615720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28042

American (AMR)

AF:

0.00

AC:

AN:

18534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18834

East Asian (EAS)

AF:

0.00

AC:

AN:

34152

South Asian (SAS)

AF:

0.00

AC:

AN:

58334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

9.77e-7

AC:

AN:

1023110

Other (OTH)

AF:

0.00

AC:

AN:

52866

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.019

T;.

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.11

T;T

PhyloP100

0.56

PrimateAI

Benign

0.41

Sift4G

Benign

0.088

T;D

Polyphen

0.018

B;.

Vest4

0.12

MVP

0.26

GERP RS

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.098

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over