rs769495113
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032444.4(SLX4):āc.1537T>Cā(p.Trp513Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,518 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 (ā ā ).
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.1537T>C | p.Trp513Arg | missense_variant | 7/15 | ENST00000294008.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.1537T>C | p.Trp513Arg | missense_variant | 7/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.2758T>C | non_coding_transcript_exon_variant | 5/7 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151668Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251386Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135908
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151668Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74054
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.1537T>C (p.W513R) alteration is located in exon 7 (coding exon 6) of the SLX4 gene. This alteration results from a T to C substitution at nucleotide position 1537, causing the tryptophan (W) at amino acid position 513 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 2023 | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 513 of the SLX4 protein (p.Trp513Arg). This variant is present in population databases (rs769495113, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 576434). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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