rs201279467
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_032444.4(SLX4):c.2628C>T(p.Asp876=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,614,168 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 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
SLX4
NM_032444.4 synonymous
NM_032444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.58
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 -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 16-3591010-G-A is Benign according to our data. Variant chr16-3591010-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3591010-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.58 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00023 (35/152330) while in subpopulation EAS AF= 0.00482 (25/5184). AF 95% confidence interval is 0.00335. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| SLX4 | NM_032444.4 | c.2628C>T | p.Asp876= | synonymous_variant | 12/15 | ENST00000294008.4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLX4 | ENST00000294008.4 | c.2628C>T | p.Asp876= | synonymous_variant | 12/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000390 AC: 98AN: 251394Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135882
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GnomAD4 exome AF: 0.000166 AC: 242AN: 1461838Hom.: 0 Cov.: 36 AF XY: 0.000157 AC XY: 114AN XY: 727224
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GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group P Benign:2
| Likely benign, 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 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. - |
| Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not specified Benign:1
| Likely benign, no assertion criteria provided | curation | Leiden Open Variation Database | Aug 31, 2012 | Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. - |
Fanconi anemia Benign:1
| Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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