16-3591279-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_032444.4(SLX4):c.2359G>A(p.Glu787Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,612,302 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00122 AC: 185AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00126 AC: 315AN: 249766Hom.: 0 AF XY: 0.00141 AC XY: 190AN XY: 135222
GnomAD4 exome AF: 0.00116 AC: 1694AN: 1459998Hom.: 3 Cov.: 36 AF XY: 0.00117 AC XY: 848AN XY: 726424
GnomAD4 genome AF: 0.00121 AC: 185AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.00120 AC XY: 89AN XY: 74474
ClinVar
Submissions by phenotype
Fanconi anemia complementation group P Uncertain:2Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Uncertain:2Benign:1
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SLX4: BP4 -
Published functional studies demonstrate cell growth similar to wild-type following exposure to Mitomycin C (PMID: 22911665); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast or ovarian cancer, but also in unaffected controls (PMID: 23211700, 22911665, 32546565); Observed in the homozygous state in a cohort of men with infertility (PMID: 36041235); This variant is associated with the following publications: (PMID: 23211700, 22911665, 23840564, 28678401, 32546565, 34426522, 36041235) -
not specified Uncertain:1Benign:1
Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -
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Fanconi anemia Benign:2
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SLX4-related disorder Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at