rs577770118
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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):āc.5403G>Cā(p.Leu1801=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,946 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 (ā ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 33)
Exomes š: 0.000023 ( 0 hom. )
Consequence
SLX4
NM_032444.4 synonymous
NM_032444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.48
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=-0.49).
BP6
?
Variant 16-3582444-C-G is Benign according to our data. Variant chr16-3582444-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 526497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.48 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000233 (34/1461610) while in subpopulation AFR AF= 0.000926 (31/33480). AF 95% confidence interval is 0.00067. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.5403G>C | p.Leu1801= | synonymous_variant | 15/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.5403G>C | p.Leu1801= | synonymous_variant | 15/15 | ||
SLX4 | XM_011522715.4 | c.5400G>C | p.Leu1800= | synonymous_variant | 15/15 | ||
SLX4 | XM_047434801.1 | c.4401G>C | p.Leu1467= | synonymous_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.5403G>C | p.Leu1801= | synonymous_variant | 15/15 | 5 | NM_032444.4 | P1 | |
ENST00000573982.1 | n.199-692C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250190Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135420
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461610Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727118
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GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 07, 2020 | - - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2022 | - - |
Fanconi anemia complementation group P Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 11, 2021 | - - |
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