rs111738042
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_032444.4(SLX4):āc.5501A>Gā(p.Asn1834Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 1,611,090 control chromosomes in the GnomAD database, including 45 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.5501A>G | p.Asn1834Ser | missense_variant | 15/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.5501A>G | p.Asn1834Ser | missense_variant | 15/15 | ||
SLX4 | XM_011522715.4 | c.5498A>G | p.Asn1833Ser | missense_variant | 15/15 | ||
SLX4 | XM_047434801.1 | c.4499A>G | p.Asn1500Ser | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.5501A>G | p.Asn1834Ser | missense_variant | 15/15 | 5 | NM_032444.4 | P1 | |
ENST00000573982.1 | n.199-790T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00564 AC: 859AN: 152220Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00558 AC: 1388AN: 248708Hom.: 6 AF XY: 0.00566 AC XY: 764AN XY: 134906
GnomAD4 exome AF: 0.00775 AC: 11302AN: 1458754Hom.: 43 Cov.: 32 AF XY: 0.00754 AC XY: 5475AN XY: 725810
GnomAD4 genome ? AF: 0.00564 AC: 859AN: 152336Hom.: 2 Cov.: 33 AF XY: 0.00546 AC XY: 407AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | SLX4: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 21, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2021 | This variant is associated with the following publications: (PMID: 28051113, 28717660, 22401137, 28202063, 21805310) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2016 | - - |
Likely benign, no assertion criteria provided | curation | Leiden Open Variation Database | Aug 31, 2012 | Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Apr 19, 2017 | BS1,BP4,BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). - |
Fanconi anemia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 02, 2021 | - - |
Fanconi anemia complementation group P Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at