rs151001222
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_144991.3(TSPEAR):c.170G>A(p.Arg57Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,605,430 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144991.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.170G>A | p.Arg57Gln | missense_variant | 2/12 | ENST00000323084.9 | NP_659428.2 | |
TSPEAR | NM_001272037.2 | c.-35G>A | 5_prime_UTR_variant | 3/13 | NP_001258966.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.170G>A | p.Arg57Gln | missense_variant | 2/12 | 1 | NM_144991.3 | ENSP00000321987 | P1 | |
TSPEAR | ENST00000397916.1 | n.125G>A | non_coding_transcript_exon_variant | 2/11 | 1 | |||||
TSPEAR | ENST00000642437.1 | c.*115G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/13 | ENSP00000496535 |
Frequencies
GnomAD3 genomes AF: 0.00191 AC: 291AN: 152114Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000545 AC: 134AN: 245710Hom.: 1 AF XY: 0.000444 AC XY: 59AN XY: 132896
GnomAD4 exome AF: 0.000242 AC: 351AN: 1453198Hom.: 6 Cov.: 30 AF XY: 0.000237 AC XY: 171AN XY: 722466
GnomAD4 genome AF: 0.00192 AC: 292AN: 152232Hom.: 1 Cov.: 32 AF XY: 0.00191 AC XY: 142AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 22, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2024 | The c.170G>A (p.R57Q) alteration is located in exon 2 (coding exon 2) of the TSPEAR gene. This alteration results from a G to A substitution at nucleotide position 170, causing the arginine (R) at amino acid position 57 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Arg57Gln in exon 2 of TSPEAR: This variant is not expected to have clinical sign ificance because it has been identified in 0.6% (26/4406) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs151001222). - |
TSPEAR-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2020 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at