rs148547201
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_032444.4(SLX4):c.742G>A(p.Glu248Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,614,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E248Q) has been classified 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.742G>A | p.Glu248Lys | missense_variant | 3/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.742G>A | p.Glu248Lys | missense_variant | 3/15 | ||
SLX4 | XM_011522715.4 | c.742G>A | p.Glu248Lys | missense_variant | 3/15 | ||
SLX4 | XR_007064923.1 | n.1391G>A | non_coding_transcript_exon_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.742G>A | p.Glu248Lys | missense_variant | 3/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.1037G>A | non_coding_transcript_exon_variant | 2/7 | 1 | ||||
SLX4 | ENST00000486524.1 | n.1370G>A | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
SLX4 | ENST00000697858.1 | n.83G>A | non_coding_transcript_exon_variant | 1/3 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000288 AC: 72AN: 250260Hom.: 0 AF XY: 0.000295 AC XY: 40AN XY: 135372
GnomAD4 exome AF: 0.000414 AC: 605AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 294AN XY: 727242
GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74518
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 11, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 27, 2016 | - - |
Fanconi anemia complementation group P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 16, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at