ENST00000612748.1:c.2040C>A

Variant names:

• chr7-94665370-C-A
• rs3750105
• ENST00000612748.1:c.2040C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000612748.1(PEG10):​c.2040C>A​(p.Ile680Ile) variant causes a synonymous 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. 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 ENST00000612748.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.239 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000612748.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEG10	NM_001172437.2		c.2042C>A	p.Ser681Tyr	missense	Exon 2 of 2	NP_001165908.1	Q86TG7-4
	PEG10	NM_001184961.1		c.1916C>A	p.Ser639Tyr	missense	Exon 2 of 2	NP_001171890.1	Q86TG7
	PEG10	NM_015068.3		c.1814C>A	p.Ser605Tyr	missense	Exon 2 of 2	NP_055883.2	Q86TG7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEG10	ENST00000612748.1	TSL:5	c.2040C>A	p.Ile680Ile	synonymous	Exon 3 of 3	ENSP00000480676.1	A0A087WX23
	PEG10	ENST00000615790.5	TSL:1	c.*836C>A		3_prime_UTR	Exon 2 of 2	ENSP00000482653.2	Q86TG7-3
	PEG10	ENST00000482108.1	TSL:1	c.*836C>A		3_prime_UTR	Exon 2 of 2	ENSP00000417587.1	Q86TG7-2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17973 AN: 151988 Hom.: 1397 Cov.: 32

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

GnomAD2 exomes AF: 0.162 AC: 25526 AN: 157788 AF XY: 0.166

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 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.: 0 AF XY: 0.160 AC XY: 48821 AN XY: 305638

African (AFR) AF: 0.0246 AC: 389 AN: 15812

American (AMR) AF: 0.162 AC: 5638 AN: 34722

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 2689 AN: 20030

East Asian (EAS) AF: 0.233 AC: 7489 AN: 32110

South Asian (SAS) AF: 0.235 AC: 14734 AN: 62776

European-Finnish (FIN) AF: 0.205 AC: 10076 AN: 49114

Middle Eastern (MID) AF: 0.143 AC: 584 AN: 4082

European-Non Finnish (NFE) AF: 0.133 AC: 42304 AN: 317160

Other (OTH) AF: 0.136 AC: 4184 AN: 30806

GnomAD4 genome AF: 0.118 AC: 17965 AN: 152106 Hom.: 1402 Cov.: 32 AF XY: 0.125 AC XY: 9311 AN XY: 74326

African (AFR) AF: 0.0260 AC: 1080 AN: 41526

American (AMR) AF: 0.152 AC: 2328 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1175 AN: 5160

South Asian (SAS) AF: 0.244 AC: 1174 AN: 4810

European-Finnish (FIN) AF: 0.213 AC: 2250 AN: 10556

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9041 AN: 67976

Other (OTH) AF: 0.115 AC: 243 AN: 2108

Alfa AF: 0.129 Hom.: 4378

Bravo AF: 0.109

Asia WGS AF: 0.194 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.8
DANN	Benign	0.85
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3750105; hg19: chr7-94294682; COSMIC: COSV71788320; COSMIC: COSV71788320;