rs756720856
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_032444.4(SLX4):āc.192A>Gā(p.Lys64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.000051 ( 0 hom. )
Consequence
SLX4
NM_032444.4 synonymous
NM_032444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.40
Genes affected
SLX4 (HGNC:23845): (SLX4 structure-specific endonuclease subunit) This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 16-3608773-T-C is Benign according to our data. Variant chr16-3608773-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 456292.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=1.39 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.192A>G | p.Lys64= | synonymous_variant | 2/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.192A>G | p.Lys64= | synonymous_variant | 2/15 | ||
SLX4 | XM_011522715.4 | c.192A>G | p.Lys64= | synonymous_variant | 2/15 | ||
SLX4 | XR_007064923.1 | n.841A>G | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.192A>G | p.Lys64= | synonymous_variant | 2/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.487A>G | non_coding_transcript_exon_variant | 1/7 | 1 | ||||
SLX4 | ENST00000486524.1 | n.820A>G | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
SLX4 | ENST00000697859.1 | n.814A>G | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251496Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135922
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GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727248
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Fanconi anemia complementation group P Uncertain:1
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. - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | SLX4: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at