7-94665370-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001172437.2(PEG10):​c.2042C>T​(p.Ser681Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000882 in 566,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: PEG10 NM_001172437.2 missense
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172437.2. 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>T	p.Ser681Phe	missense	Exon 2 of 2	NP_001165908.1	Q86TG7-4
	PEG10	NM_001184961.1		c.1916C>T	p.Ser639Phe	missense	Exon 2 of 2	NP_001171890.1	Q86TG7
	PEG10	NM_015068.3		c.1814C>T	p.Ser605Phe	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>T	p.Ile680Ile	synonymous	Exon 3 of 3	ENSP00000480676.1	A0A087WX23
	PEG10	ENST00000615790.5	TSL:1	c.*836C>T		3_prime_UTR	Exon 2 of 2	ENSP00000482653.2	Q86TG7-3
	PEG10	ENST00000482108.1	TSL:1	c.*836C>T		3_prime_UTR	Exon 2 of 2	ENSP00000417587.1	Q86TG7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000882 AC: 5 AN: 566618 Hom.: 0 Cov.: 0 AF XY: 0.00000327 AC XY: 1 AN XY: 305640

African (AFR) AF: 0.0000632 AC: 1 AN: 15812

American (AMR) AF: 0.00 AC: 0 AN: 34722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20030

East Asian (EAS) AF: 0.00 AC: 0 AN: 32110

South Asian (SAS) AF: 0.00 AC: 0 AN: 62776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49120

Middle Eastern (MID) AF: 0.000735 AC: 3 AN: 4082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 317160

Other (OTH) AF: 0.0000325 AC: 1 AN: 30806

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.2
DANN	Benign	0.88
PhyloP100		-0.24

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;