rs745485209
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032444.4(SLX4):c.4371G>T(p.Arg1457Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R1457R) has been classified as Likely benign.
Frequency
Consequence
NM_032444.4 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 |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.4371G>T | p.Arg1457Ser | missense_variant | 12/15 | ENST00000294008.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.4371G>T | p.Arg1457Ser | missense_variant | 12/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000826 AC: 2AN: 242028Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130794
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1448718Hom.: 0 Cov.: 38 AF XY: 0.00000556 AC XY: 4AN XY: 718794
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs745485209, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1457 of the SLX4 protein (p.Arg1457Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at