GeneBe

rs62218852

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The ENST00000323084.9(TSPEAR):​c.1698C>T​(p.Tyr566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,614,002 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

TSPEAR
ENST00000323084.9 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.613
Variant links:
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]
TSPEAR-AS1 (HGNC:1271): (TSPEAR antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 21-44509255-G-A is Benign according to our data. Variant chr21-44509255-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 504824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.613 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSPEARNM_144991.3 linkuse as main transcriptc.1698C>T p.Tyr566= synonymous_variant 10/12 ENST00000323084.9 NP_659428.2
TSPEAR-AS1NR_103707.1 linkuse as main transcriptn.1218G>A non_coding_transcript_exon_variant 5/7
TSPEARNM_001272037.2 linkuse as main transcriptc.1494C>T p.Tyr498= synonymous_variant 11/13 NP_001258966.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSPEARENST00000323084.9 linkuse as main transcriptc.1698C>T p.Tyr566= synonymous_variant 10/121 NM_144991.3 ENSP00000321987 P1Q8WU66-1
TSPEARENST00000397916.1 linkuse as main transcriptn.1653C>T non_coding_transcript_exon_variant 10/111
TSPEAR-AS1ENST00000451035.2 linkuse as main transcriptn.773G>A non_coding_transcript_exon_variant 4/65
TSPEARENST00000642437.1 linkuse as main transcriptc.*1643C>T 3_prime_UTR_variant, NMD_transcript_variant 11/13 ENSP00000496535

Frequencies

GnomAD3 genomes
AF:
0.000473
AC:
72
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00255
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000446
AC:
112
AN:
251372
Hom.:
0
AF XY:
0.000419
AC XY:
57
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000624
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000613
AC:
896
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.000573
AC XY:
417
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000721
Gnomad4 OTH exome
AF:
0.000695
GnomAD4 genome
AF:
0.000473
AC:
72
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.000525
AC XY:
39
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00255
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000442
Hom.:
0
Bravo
AF:
0.000525
EpiCase
AF:
0.000654
EpiControl
AF:
0.000771

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 30, 2021- -
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsJul 26, 2019- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 13, 2023- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJun 07, 2016p.Tyr566Tyr in exon 10 of TSPEAR: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 24/66374 Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs62218852). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
CADD
Benign
6.3
DANN
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62218852; hg19: chr21-45929138; API