21-44499821-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144991.3(TSPEAR):c.1972G>A(p.Glu658Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,430 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 (★).
Frequency
Consequence
NM_144991.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.1972G>A | p.Glu658Lys | missense_variant | Exon 12 of 12 | 1 | NM_144991.3 | ENSP00000321987.4 | ||
TSPEAR | ENST00000642437.1 | n.*1917G>A | non_coding_transcript_exon_variant | Exon 13 of 13 | ENSP00000496535.1 | |||||
TSPEAR | ENST00000642437.1 | n.*1917G>A | 3_prime_UTR_variant | Exon 13 of 13 | ENSP00000496535.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000509 AC: 1AN: 196414Hom.: 0 AF XY: 0.00000942 AC XY: 1AN XY: 106194
GnomAD4 exome AF: 6.99e-7 AC: 1AN: 1430430Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 708854
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 658 of the TSPEAR protein (p.Glu658Lys). This variant is present in population databases (rs782425063, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TSPEAR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at