rs757069991
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032444.4(SLX4):c.565C>T(p.Pro189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,876 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 (★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.565C>T | p.Pro189Ser | missense_variant | 3/15 | ENST00000294008.4 | NP_115820.2 | |
SLX4 | XM_024450471.2 | c.565C>T | p.Pro189Ser | missense_variant | 3/15 | XP_024306239.1 | ||
SLX4 | XM_011522715.4 | c.565C>T | p.Pro189Ser | missense_variant | 3/15 | XP_011521017.1 | ||
SLX4 | XR_007064923.1 | n.1214C>T | non_coding_transcript_exon_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.565C>T | p.Pro189Ser | missense_variant | 3/15 | 5 | NM_032444.4 | ENSP00000294008 | P1 | |
SLX4 | ENST00000466154.5 | n.860C>T | non_coding_transcript_exon_variant | 2/7 | 1 | |||||
SLX4 | ENST00000486524.1 | n.1193C>T | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251432Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 07, 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs757069991, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 189 of the SLX4 protein (p.Pro189Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at