chr16-3597971-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_032444.4(SLX4):c.1192C>T(p.Arg398Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R398Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
Publications
- Fanconi anemia complementation group PInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
- Fanconi anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000358 AC: 9AN: 251382 AF XY: 0.0000368 show subpopulations
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461834Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26AN XY: 727216 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74334 show subpopulations
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 398 of the SLX4 protein (p.Arg398Trp). This variant is present in population databases (rs138799572, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 407916). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Fanconi anemia complementation group P Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at