rs13226637

Variant names:

• chr7-94667481-C-T
• rs13226637
• ENST00000615790.5:c.*2947C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615790.5(PEG10):​c.*2947C>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 ENST00000615790.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
PEG10	NM_001172437.2	c.*1799C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001165908.1
PEG10	NM_001184961.1	c.*1799C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001171890.1
PEG10	NM_015068.3	c.*1799C>T		3_prime_UTR_variant	Exon 2 of 2		NP_055883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEG10	ENST00000615790.5	c.*2947C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000482653.2
PEG10	ENST00000482108.1	c.*2947C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000417587.1
PEG10	ENST00000612941.2	c.*1799C>T		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000478744.2

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.210 AC: 3078 AN: 14668

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.214 AC: 18 AN: 84

Other (OTH) AF: 0.222 AC: 20 AN: 90

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

African (AFR) AF: 0.116 AC: 4827 AN: 41510

American (AMR) AF: 0.162 AC: 2479 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1177 AN: 5182

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2256 AN: 10584

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9064 AN: 68018

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.135 Hom.: 2455

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
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs13226637; hg19: chr7-94296793;