rs199838670
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_032444.4(SLX4):āc.5188T>Cā(p.Ser1730Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,612,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1730C) has been classified as Uncertain significance.
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.5188T>C | p.Ser1730Pro | missense_variant | 15/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.5188T>C | p.Ser1730Pro | missense_variant | 15/15 | ||
SLX4 | XM_011522715.4 | c.5185T>C | p.Ser1729Pro | missense_variant | 15/15 | ||
SLX4 | XM_047434801.1 | c.4186T>C | p.Ser1396Pro | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.5188T>C | p.Ser1730Pro | missense_variant | 15/15 | 5 | NM_032444.4 | P1 | |
ENST00000573982.1 | n.199-477A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152062Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249220Hom.: 1 AF XY: 0.0000593 AC XY: 8AN XY: 134990
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460864Hom.: 1 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 726824
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152062Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74278
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 09, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 01, 2022 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1730 of the SLX4 protein (p.Ser1730Pro). This variant is present in population databases (rs199838670, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 456332). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Fanconi anemia complementation group P Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 22, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 | Jul 17, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31469826, 32546565) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at