rs1809248449

Variant names:

• chr7-94663367-G-C
• rs1809248449
• ENST00000612748.1:c.39G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-94663367-G-C
• chr7-94663367-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172437.2(PEG10):​c.39G>C​(p.Arg13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEG10 NM_001172437.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.563
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10325074).

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.39G>C	p.Arg13Ser	missense	Exon 2 of 2	NP_001165908.1	Q86TG7-4
	PEG10	NM_001172438.3		c.39G>C	p.Arg13Ser	missense	Exon 2 of 2	NP_001165909.1	Q86TG7-5
	PEG10	NM_001184961.1		c.-88G>C		5_prime_UTR	Exon 2 of 2	NP_001171890.1	Q86TG7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEG10	ENST00000612748.1	TSL:5	c.39G>C	p.Arg13Ser	missense	Exon 2 of 3	ENSP00000480676.1	A0A087WX23
	PEG10	ENST00000615790.5	TSL:1	c.-88G>C		5_prime_UTR	Exon 2 of 2	ENSP00000482653.2	Q86TG7-3
	PEG10	ENST00000482108.1	TSL:1	c.-190G>C		5_prime_UTR	Exon 2 of 2	ENSP00000417587.1	Q86TG7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	21
DANN	Benign	0.82
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.10	T
PhyloP100		0.56
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.088	T
Polyphen		0.018	B
Vest4		0.12
MVP		0.26
GERP RS		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.098
Mutation Taster		=300/0	polymorphism

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: rs1809248449; hg19: chr7-94292679;