chr21-44499799-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_144991.3(TSPEAR):c.1994G>A(p.Arg665Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,572,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R665W) has been classified as Uncertain significance.
Frequency
Consequence
NM_144991.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.1994G>A | p.Arg665Gln | missense_variant | 12/12 | ENST00000323084.9 | |
TSPEAR | NM_001272037.2 | c.1790G>A | p.Arg597Gln | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.1994G>A | p.Arg665Gln | missense_variant | 12/12 | 1 | NM_144991.3 | P1 | |
TSPEAR | ENST00000642437.1 | c.*1939G>A | 3_prime_UTR_variant, NMD_transcript_variant | 13/13 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000219 AC: 4AN: 182650Hom.: 0 AF XY: 0.0000407 AC XY: 4AN XY: 98388
GnomAD4 exome AF: 0.0000585 AC: 83AN: 1419994Hom.: 0 Cov.: 31 AF XY: 0.0000612 AC XY: 43AN XY: 702700
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at