21-44533884-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_144991.3(TSPEAR):c.343G>A(p.Asp115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000974 in 1,611,820 control chromosomes in the GnomAD database, including 11 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D115D) has been classified as Likely benign.
Frequency
Consequence
NM_144991.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.343G>A | p.Asp115Asn | missense_variant | 3/12 | ENST00000323084.9 | |
TSPEAR | NM_001272037.2 | c.139G>A | p.Asp47Asn | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.343G>A | p.Asp115Asn | missense_variant | 3/12 | 1 | NM_144991.3 | P1 | |
TSPEAR | ENST00000397916.1 | n.298G>A | non_coding_transcript_exon_variant | 3/11 | 1 | ||||
TSPEAR | ENST00000642437.1 | c.*288G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/13 |
Frequencies
GnomAD3 genomes AF: 0.00182 AC: 275AN: 151440Hom.: 1 Cov.: 29
GnomAD3 exomes AF: 0.00118 AC: 290AN: 246454Hom.: 0 AF XY: 0.00118 AC XY: 159AN XY: 134350
GnomAD4 exome AF: 0.000882 AC: 1288AN: 1460264Hom.: 9 Cov.: 33 AF XY: 0.000887 AC XY: 644AN XY: 726438
GnomAD4 genome AF: 0.00186 AC: 282AN: 151556Hom.: 2 Cov.: 29 AF XY: 0.00192 AC XY: 142AN XY: 73990
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 26, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | TSPEAR: BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 23, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 31, 2019 | - - |
TSPEAR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 13, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Asp115Asn in exon 3 of TSPEAR: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (20/4388) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs144586270). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at