21-44499859-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144991.3(TSPEAR):c.1934C>T(p.Thr645Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000312 in 1,603,602 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
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TSPEAR
NM_144991.3 missense
NM_144991.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09453595).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.1934C>T | p.Thr645Ile | missense_variant | 12/12 | ENST00000323084.9 | NP_659428.2 | |
TSPEAR | NM_001272037.2 | c.1730C>T | p.Thr577Ile | missense_variant | 13/13 | NP_001258966.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.1934C>T | p.Thr645Ile | missense_variant | 12/12 | 1 | NM_144991.3 | ENSP00000321987.4 | ||
TSPEAR | ENST00000642437.1 | n.*1879C>T | non_coding_transcript_exon_variant | 13/13 | ENSP00000496535.1 | |||||
TSPEAR | ENST00000642437.1 | n.*1879C>T | 3_prime_UTR_variant | 13/13 | ENSP00000496535.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000176 AC: 4AN: 227394Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124062
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GnomAD4 exome AF: 0.00000207 AC: 3AN: 1451258Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 721146
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74500
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
.;T
Polyphen
P;P
Vest4
0.47
MutPred
Loss of glycosylation at S644 (P = 0.0745);Loss of glycosylation at S644 (P = 0.0745);
MVP
MPC
0.087
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at