rs199940702
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_025074.7(FRAS1):c.3700G>A(p.Ala1234Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,613,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_025074.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/74 | ENST00000512123.4 | |
FRAS1 | NM_001166133.2 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000325942.11 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/42 | 1 | |||
FRAS1 | ENST00000682513.1 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/64 | ||||
FRAS1 | ENST00000684159.1 | c.3700G>A | p.Ala1234Thr | missense_variant | 29/45 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 151930Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000217 AC: 54AN: 248696Hom.: 0 AF XY: 0.000274 AC XY: 37AN XY: 134912
GnomAD4 exome AF: 0.000273 AC: 399AN: 1461344Hom.: 0 Cov.: 31 AF XY: 0.000301 AC XY: 219AN XY: 726946
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152048Hom.: 0 Cov.: 31 AF XY: 0.000202 AC XY: 15AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 01, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1234 of the FRAS1 protein (p.Ala1234Thr). This variant is present in population databases (rs199940702, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with FRAS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 221949). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Rieger anomaly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Paul Sabatier University EA-4555, Paul Sabatier University | Jan 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at