rs199573277
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032444.4(SLX4):c.4883C>T(p.Thr1628Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,272 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1628N) has been classified as Uncertain significance.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.4883C>T | p.Thr1628Ile | missense_variant | 14/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.4883C>T | p.Thr1628Ile | missense_variant | 14/15 | ||
SLX4 | XM_011522715.4 | c.4880C>T | p.Thr1627Ile | missense_variant | 14/15 | ||
SLX4 | XM_047434801.1 | c.3881C>T | p.Thr1294Ile | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.4883C>T | p.Thr1628Ile | missense_variant | 14/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251140Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135732
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460918Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726614
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74492
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 18, 2023 | This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs199573277, gnomAD 0.04%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1628 of the SLX4 protein (p.Thr1628Ile). ClinVar contains an entry for this variant (Variation ID: 526400). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at