chr21-44504850-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144991.3(TSPEAR):c.1786G>A(p.Glu596Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E596D) has been classified 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.1786G>A | p.Glu596Lys | missense_variant | 11/12 | ENST00000323084.9 | |
TSPEAR | NM_001272037.2 | c.1582G>A | p.Glu528Lys | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.1786G>A | p.Glu596Lys | missense_variant | 11/12 | 1 | NM_144991.3 | P1 | |
TSPEAR | ENST00000642437.1 | c.*1731G>A | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151904Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251434Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135892
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727160
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151904Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74162
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 30, 2015 | The p.Glu596Lys variant in TSPEAR has not been previously reported in individual s with hearing loss, but has been identified in 4/11548 of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Althou gh this variant has been seen in the general population, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analyses suggest that the p.Glu596Lys variant may impact the protein, t hough this information is not predictive enough to determine pathogenicity. In s ummary, the clinical significance of the p.Glu596Lys variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at