chr16-3594590-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_032444.4(SLX4):c.2023G>A(p.Gly675Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,932 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 nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.2023G>A | p.Gly675Arg | missense_variant | 10/15 | ENST00000294008.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.2023G>A | p.Gly675Arg | missense_variant | 10/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251206Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135830
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727204
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | 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 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. ClinVar contains an entry for this variant (Variation ID: 526399). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs767473953, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 675 of the SLX4 protein (p.Gly675Arg). - |
Fanconi anemia complementation group P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 20, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at