chr16-3590529-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032444.4(SLX4):āc.3109T>Cā(p.Leu1037=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,078 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0019 ( 2 hom., cov: 33)
Exomes š: 0.0015 ( 35 hom. )
Consequence
SLX4
NM_032444.4 synonymous
NM_032444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.930
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 16-3590529-A-G is Benign according to our data. Variant chr16-3590529-A-G is described in ClinVar as [Benign]. Clinvar id is 414702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3590529-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.93 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00188 (286/152262) while in subpopulation EAS AF= 0.0323 (167/5170). AF 95% confidence interval is 0.0283. There are 2 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.3109T>C | p.Leu1037= | synonymous_variant | 12/15 | ENST00000294008.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.3109T>C | p.Leu1037= | synonymous_variant | 12/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00189 AC: 287AN: 152144Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00307 AC: 772AN: 251072Hom.: 10 AF XY: 0.00289 AC XY: 393AN XY: 135764
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GnomAD4 exome AF: 0.00152 AC: 2225AN: 1460816Hom.: 35 Cov.: 37 AF XY: 0.00152 AC XY: 1103AN XY: 726474
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GnomAD4 genome AF: 0.00188 AC: 286AN: 152262Hom.: 2 Cov.: 33 AF XY: 0.00251 AC XY: 187AN XY: 74456
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group P Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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