rs143540691
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001365999.1(SZT2):c.6920C>T(p.Ala2307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2307A) has been classified as Likely benign.
Frequency
Consequence
NM_001365999.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.6920C>T | p.Ala2307Val | missense_variant | 50/72 | ENST00000634258.3 | |
SZT2 | NM_015284.4 | c.6749C>T | p.Ala2250Val | missense_variant | 49/71 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.6920C>T | p.Ala2307Val | missense_variant | 50/72 | 5 | NM_001365999.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250344Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135446
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461388Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 726984
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | This variant has not been reported in the literature in individuals affected with SZT2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SZT2 protein function. ClinVar contains an entry for this variant (Variation ID: 411943). This variant is present in population databases (rs143540691, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2250 of the SZT2 protein (p.Ala2250Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at