rs543584983
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002354.3(EPCAM):c.111C>G(p.Asn37Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002354.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPCAM | NM_002354.3 | c.111C>G | p.Asn37Lys | missense_variant | 2/9 | ENST00000263735.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPCAM | ENST00000263735.9 | c.111C>G | p.Asn37Lys | missense_variant | 2/9 | 1 | NM_002354.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251168Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135780
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461232Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 726986
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74266
ClinVar
Submissions by phenotype
Lynch syndrome 8 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Apr 19, 2016 | - - |
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces asparagine with lysine at codon 37 of the EPCAM protein (p.Asn37Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs543584983, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with EPCAM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at