7-94667457-T-C

Variant names:

• chr7-94667457-T-C
• rs13073
• ENST00000615790.5:c.*2923T>C

Variant summary

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

The ENST00000615790.5(PEG10):​c.*2923T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 167,110 control chromosomes in the GnomAD database, including 52,226 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 0.78 (47514 hom., cov: 33)
  • Exomes 𝑓: 0.80 (4712 hom.)
• Consequence: PEG10 ENST00000615790.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 24 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEG10	NM_001172437.2	c.*1775T>C		3_prime_UTR_variant	Exon 2 of 2		NP_001165908.1
PEG10	NM_001184961.1	c.*1775T>C		3_prime_UTR_variant	Exon 2 of 2		NP_001171890.1
PEG10	NM_015068.3	c.*1775T>C		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.*2923T>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000482653.2
PEG10	ENST00000482108.1	c.*2923T>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000417587.1
PEG10	ENST00000612941.2	c.*1775T>C		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000478744.2

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119228 AN: 152116 Hom.: 47462 Cov.: 33

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.796 AC: 11837 AN: 14876 Hom.: 4712 Cov.: 0 AF XY: 0.792 AC XY: 5594 AN XY: 7060

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.796 AC: 11697 AN: 14688

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

European-Non Finnish (NFE) AF: 0.762 AC: 64 AN: 84

Other (OTH) AF: 0.722 AC: 65 AN: 90

GnomAD4 genome AF: 0.784 AC: 119337 AN: 152234 Hom.: 47514 Cov.: 33 AF XY: 0.785 AC XY: 58423 AN XY: 74414

African (AFR) AF: 0.923 AC: 38353 AN: 41560

American (AMR) AF: 0.727 AC: 11123 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3923 AN: 5172

South Asian (SAS) AF: 0.642 AC: 3097 AN: 4826

European-Finnish (FIN) AF: 0.803 AC: 8509 AN: 10592

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.722 AC: 49084 AN: 68000

Other (OTH) AF: 0.754 AC: 1595 AN: 2116

Alfa AF: 0.742 Hom.: 69925

Bravo AF: 0.786

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.37
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: rs13073; hg19: chr7-94296769;