rs796051875
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_020223.4(FAM20C):c.796G>A(p.Gly266Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G266W) has been classified as Uncertain significance.
Frequency
Consequence
NM_020223.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM20C | NM_020223.4 | c.796G>A | p.Gly266Arg | missense_variant | 3/10 | ENST00000313766.6 | |
FAM20C | XR_007060116.1 | n.1425G>A | non_coding_transcript_exon_variant | 3/7 | |||
FAM20C | XR_001744837.2 | n.1413+13177G>A | intron_variant, non_coding_transcript_variant | ||||
FAM20C | XR_007060117.1 | n.1413+13177G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM20C | ENST00000313766.6 | c.796G>A | p.Gly266Arg | missense_variant | 3/10 | 1 | NM_020223.4 | P1 | |
FAM20C | ENST00000477004.1 | n.277G>A | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000140 AC: 2AN: 1424616Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2AN XY: 704890
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
Lethal osteosclerotic bone dysplasia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2009 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 266 of the FAM20C protein (p.Gly266Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with Raine syndrome (PMID: 19250384). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30877). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FAM20C protein function. 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