16-3600992-GGCT-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_032444.4(SLX4):βc.1147_1149delβ(p.Ser383del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 31)
Exomes π: 0.0000041 ( 0 hom. )
Consequence
SLX4
NM_032444.4 inframe_deletion
NM_032444.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.08
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_032444.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.1147_1149del | p.Ser383del | inframe_deletion | 5/15 | ENST00000294008.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.1147_1149del | p.Ser383del | inframe_deletion | 5/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.2368_2370del | non_coding_transcript_exon_variant | 3/7 | 1 | ||||
SLX4 | ENST00000486524.1 | n.2701_2703del | non_coding_transcript_exon_variant | 4/4 | 2 | ||||
SLX4 | ENST00000697858.1 | n.488_490del | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461474Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727036
GnomAD4 exome
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1461474
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3
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 19, 2015 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with SLX4-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.1147_1149del, results in the deletion of 1 amino acid(s) of the SLX4 protein (p.Ser383del), but otherwise preserves the integrity of the reading frame. - |
Fanconi anemia complementation group P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 30, 2021 | - - |
Computational scores
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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