rs13226637

chr7-94667481-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172437.2(PEG10):c.*1800C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 167,060 control chromosomes in the GnomAD database, including 2,019 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 0.14 (1697 hom., cov: 33)
  • Exomes 𝑓: 0.21 (322 hom.)
• Consequence: PEG10 NM_001172437.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• 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	MANE	UniProt
PEG10	NM_001172437.2	c.*1800C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEG10	ENST00000482108.1	c.*2947C>T		3_prime_UTR_variant	2/2	1		A2
PEG10	ENST00000615790.5	c.*2947C>T		3_prime_UTR_variant	2/2	1		A2
PEG10	ENST00000612941.2	c.*1799C>T		3_prime_UTR_variant	3/3	5		A2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21920 AN: 152086 Hom.: 1681 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.210 AC: 3119 AN: 14856 Hom.: 322 Cov.: 0 AF XY: 0.204 AC XY: 1435 AN XY: 7048

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.144 AC: 21954 AN: 152204 Hom.: 1697 Cov.: 33 AF XY: 0.151 AC XY: 11233 AN XY: 74424

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.141

Alfa AF: 0.136 Hom.: 1556

Bravo AF: 0.139

Asia WGS AF: 0.204 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	14
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs13226637; hg19: chr7-94296793;