rs1484087361
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):c.11C>T(p.Ser4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,525,832 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 (★). Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Likely benign.
Frequency
Consequence
NM_000135.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.11C>T | p.Ser4Leu | missense_variant | 1/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.11C>T | p.Ser4Leu | missense_variant | 1/43 | ||
FANCA | NM_001018112.3 | c.11C>T | p.Ser4Leu | missense_variant | 1/11 | ||
FANCA | NM_001351830.2 | c.11C>T | p.Ser4Leu | missense_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.11C>T | p.Ser4Leu | missense_variant | 1/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000291 AC: 4AN: 1373734Hom.: 0 Cov.: 31 AF XY: 0.00000442 AC XY: 3AN XY: 678806
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the FANCA protein (p.Ser4Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. 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 FANCA 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