rs138432305
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001113378.2(FANCI):c.2960C>T(p.Thr987Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T987R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001113378.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.2960C>T | p.Thr987Met | missense_variant | 27/38 | ENST00000310775.12 | |
LOC124903548 | XR_007064749.1 | n.478G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.2960C>T | p.Thr987Met | missense_variant | 27/38 | 1 | NM_001113378.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251474Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135910
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461574Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727092
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74418
ClinVar
Submissions by phenotype
Colorectal cancer Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine. | Jul 19, 2021 | The Thr987Met variant in FANCI has been reported in 1 Chinese family with autosomal dominant predisposition in familial colorectal cancer (CRC). - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 987 of the FANCI protein (p.Thr987Met). This variant is present in population databases (rs138432305, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 408238). 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: "Possibly Damaging"; 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. - |
Fanconi anemia complementation group I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at