7-94663534-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000612748.1(PEG10):c.206A>G(p.His69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,392,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
PEG10
ENST00000612748.1 missense
ENST00000612748.1 missense
Scores
10
Clinical Significance
Conservation
PhyloP100: 0.221
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06336388).
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PEG10 | NM_001172437.2 | c.206A>G | p.His69Arg | missense_variant | Exon 2 of 2 | NP_001165908.1 | ||
| PEG10 | NM_001184961.1 | c.80A>G | p.His27Arg | missense_variant | Exon 2 of 2 | NP_001171890.1 | ||
| PEG10 | NM_001172438.3 | c.206A>G | p.His69Arg | missense_variant | Exon 2 of 2 | NP_001165909.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PEG10 | ENST00000612748.1 | c.206A>G | p.His69Arg | missense_variant | Exon 2 of 3 | 5 | ENSP00000480676.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000381 AC: 6AN: 157652 AF XY: 0.0000240 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
157652
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000101 AC: 14AN: 1392426Hom.: 0 Cov.: 35 AF XY: 0.0000102 AC XY: 7AN XY: 686870 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
1392426
Hom.:
Cov.:
35
AF XY:
AC XY:
7
AN XY:
686870
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31426
American (AMR)
AF:
AC:
6
AN:
35546
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24874
East Asian (EAS)
AF:
AC:
0
AN:
35264
South Asian (SAS)
AF:
AC:
1
AN:
79174
European-Finnish (FIN)
AF:
AC:
0
AN:
47516
Middle Eastern (MID)
AF:
AC:
0
AN:
5680
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1075346
Other (OTH)
AF:
AC:
0
AN:
57600
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.446
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
May 25, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.206A>G (p.H69R) alteration is located in exon 2 (coding exon 2) of the PEG10 gene. This alteration results from a A to G substitution at nucleotide position 206, causing the histidine (H) at amino acid position 69 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
PhyloP100
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MVP
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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