Variant rs3750105 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001172437.2(PEG10):c.2042C>A(p.Ser681Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 718,718 control chromosomes in the GnomAD database, including 9,001 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1402 hom., cov: 32)

Exomes 𝑓: 0.16 ( 7599 hom. )

Consequence

PEG10
NM_001172437.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

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:

PEG10 (HGNC:):

PEG10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PEG10	NM_001172437.2 linkuse as main transcript	c.2042C>A	p.Ser681Tyr	missense_variant	2/2	NP_001165908.1	Q86TG7-4
PEG10	NM_001184961.1 linkuse as main transcript	c.1916C>A	p.Ser639Tyr	missense_variant	2/2	NP_001171890.1	Q86TG7
PEG10	NM_015068.3 linkuse as main transcript	c.1814C>A	p.Ser605Tyr	missense_variant	2/2	NP_055883.2	Q86TG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEG10	ENST00000612748.1 linkuse as main transcript	c.2040C>A	p.Ile680Ile	synonymous_variant	3/3	5		ENSP00000480676.1		A0A087WX23

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17973

AN:

151988

Hom.:

1397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.162

AC:

25526

AN:

157788

Hom.:

2327

AF XY:

0.166

AC XY:

13826

AN XY:

83356

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.155

AC:

88087

AN:

566612

Hom.:

7599

Cov.:

AF XY:

0.160

AC XY:

48821

AN XY:

305638

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.118

AC:

17965

AN:

152106

Hom.:

1402

Cov.:

AF XY:

0.125

AC XY:

9311

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.134

Hom.:

3246

Bravo

AF:

0.109

Asia WGS

AF:

0.194

AC:

677

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.8

DANN

Benign

0.85

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over