NM_001365999.1:c.9452A>G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001365999.1(SZT2):āc.9452A>Gā(p.Tyr3151Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001365999.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.9452A>G | p.Tyr3151Cys | missense_variant | Exon 68 of 72 | ENST00000634258.3 | NP_001352928.1 | |
SZT2 | NM_015284.4 | c.9281A>G | p.Tyr3094Cys | missense_variant | Exon 67 of 71 | NP_056099.3 | ||
SZT2-AS1 | NR_046744.1 | n.615T>C | non_coding_transcript_exon_variant | Exon 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251408Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135874
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727242
GnomAD4 genome AF: 0.000158 AC: 24AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74372
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 18 Uncertain:1
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not provided Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 3094 of the SZT2 protein (p.Tyr3094Cys). This variant is present in population databases (rs143392721, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SZT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043968). 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. 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. -
SZT2-related disorder Uncertain:1
The SZT2 c.9281A>G variant is predicted to result in the amino acid substitution p.Tyr3094Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.064% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-43913531-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at