rs752013105
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_032444.4(SLX4):c.4686G>T(p.Pro1562=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,040 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
SLX4
NM_032444.4 synonymous
NM_032444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.318
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 Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 16-3584822-C-A is Benign according to our data. Variant chr16-3584822-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 698994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.318 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.4686G>T | p.Pro1562= | synonymous_variant | 13/15 | ENST00000294008.4 | NP_115820.2 | |
SLX4 | XM_024450471.2 | c.4686G>T | p.Pro1562= | synonymous_variant | 13/15 | XP_024306239.1 | ||
SLX4 | XM_011522715.4 | c.4683G>T | p.Pro1561= | synonymous_variant | 13/15 | XP_011521017.1 | ||
SLX4 | XM_047434801.1 | c.3684G>T | p.Pro1228= | synonymous_variant | 9/11 | XP_047290757.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.4686G>T | p.Pro1562= | synonymous_variant | 13/15 | 5 | NM_032444.4 | ENSP00000294008 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251494Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727216
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74356
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 25, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 12, 2021 | - - |
SLX4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at