chr16-3589160-G-A
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_032444.4(SLX4):c.4478C>T(p.Ser1493Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S1493S) has been classified as Likely benign.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
Publications
- Fanconi anemia complementation group PInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
- Fanconi anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152154Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000477 AC: 12AN: 251356 AF XY: 0.0000442 show subpopulations
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461808Hom.: 0 Cov.: 39 AF XY: 0.0000124 AC XY: 9AN XY: 727210 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74458 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1493 of the SLX4 protein (p.Ser1493Leu). This variant is present in population databases (rs565491187, gnomAD 0.009%). 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: 407924). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine 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