7-94667457-T-C

Position:

• chr7-94667457-T-C

Variant summary

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

The NM_001172437.2(PEG10):​c.*1775T>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 NM_001172437.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PEG10	NM_001172437.2	c.*1775T>C		3_prime_UTR_variant	2/2		NP_001165908.1
PEG10	NM_001184961.1	c.*1775T>C		3_prime_UTR_variant	2/2		NP_001171890.1
PEG10	NM_015068.3	c.*1775T>C		3_prime_UTR_variant	2/2		NP_055883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEG10	ENST00000615790.5	c.*2923T>C		3_prime_UTR_variant	2/2	1		ENSP00000482653.2
PEG10	ENST00000482108.1	c.*2923T>C		3_prime_UTR_variant	2/2	1		ENSP00000417587.1
PEG10	ENST00000612941.2	c.*1775T>C		3_prime_UTR_variant	3/3	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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.722

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

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.754

Alfa AF: 0.737 Hom.: 48318

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
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: rs13073; hg19: chr7-94296769;