rs781868760
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_144991.3(TSPEAR):c.1852T>A(p.Tyr618Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TSPEAR
NM_144991.3 missense
NM_144991.3 missense
Scores
9
4
1
Clinical Significance
Conservation
PhyloP100: 8.25
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.946
PP5
?
Variant 21-44504784-A-T is Pathogenic according to our data. Variant chr21-44504784-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 590273.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.1852T>A | p.Tyr618Asn | missense_variant | 11/12 | ENST00000323084.9 | |
TSPEAR | NM_001272037.2 | c.1648T>A | p.Tyr550Asn | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.1852T>A | p.Tyr618Asn | missense_variant | 11/12 | 1 | NM_144991.3 | P1 | |
TSPEAR | ENST00000642437.1 | c.*1797T>A | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251280Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460728Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726760
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GnomAD4 genome ? Cov.: 30
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 05, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Polyphen
D;D
Vest4
0.99
MutPred
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
MPC
0.42
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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