rs3218611
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4_StrongBS1_Supporting
The NM_000043.6(FAS):c.914C>T(p.Thr305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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. T305A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000043.6 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 |
---|---|---|---|---|---|---|---|
FAS | NM_000043.6 | c.914C>T | p.Thr305Ile | missense_variant | 9/9 | ENST00000652046.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAS | ENST00000652046.1 | c.914C>T | p.Thr305Ile | missense_variant | 9/9 | NM_000043.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251090Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135730
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461520Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727050
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74454
ClinVar
Submissions by phenotype
Autoimmune lymphoproliferative syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | 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. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 653881). This variant has not been reported in the literature in individuals affected with FAS-related conditions. This variant is present in population databases (rs3218611, gnomAD 0.07%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 305 of the FAS protein (p.Thr305Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at