Variant chr21-44509010-TTCCCCAGGCCAGGAAAGTCCCCAGGCCATTCTTTCCACAGGAAGG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_144991.3(TSPEAR):c.1754+144_1754+188delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,495,262 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

TSPEAR
NM_144991.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51

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 links:

TSPEAR-AS1 (HGNC:1271): (TSPEAR antisense RNA 1)

TSPEAR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 21-44509010-TTCCCCAGGCCAGGAAAGTCCCCAGGCCATTCTTTCCACAGGAAGG-T is Benign according to our data. Variant chr21-44509010-TTCCCCAGGCCAGGAAAGTCCCCAGGCCATTCTTTCCACAGGAAGG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186982.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00331 (504/152180) while in subpopulation AFR AF= 0.0114 (474/41498). AF 95% confidence interval is 0.0106. There are 2 homozygotes in gnomad4. There are 240 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TSPEAR	NM_144991.3 link	c.1754+144_1754+188delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA	intron_variant	ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 link	c.1550+144_1550+188delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA	intron_variant		NP_001258966.1	Q8WU66
TSPEAR-AS1	NR_103707.1 link	n.1214+93_1214+137delGGAAAGTCCCCAGGCCATTCTTTCCACAGGAAGGTCCCCAGGCCA	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TSPEAR	ENST00000323084.9 link	c.1754+144_1754+188delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA	intron_variant	1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000397916.1 link	n.1709+144_1710-100delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA	intron_variant	1
TSPEAR-AS1	ENST00000451035.2 link	n.769+82_769+126delTCCCCAGGCCAGGAAAGTCCCCAGGCCATTCTTTCCACAGGAAGG	intron_variant	5
TSPEAR	ENST00000642437.1 link	n.1699+144_1699+188delCCTTCCTGTGGAAAGAATGGCCTGGGGACTTTCCTGGCCTGGGGA	intron_variant			ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

500

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000290

AC:

389

AN:

1343082

Hom.:

AF XY:

0.000237

AC XY:

157

AN XY:

662550

show subpopulations

Gnomad4 AFR exome

AF:

0.00956

Gnomad4 AMR exome

AF:

0.000907

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000184

Gnomad4 OTH exome

AF:

0.000754

GnomAD4 genome

AF:

0.00331

AC:

504

AN:

152180

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

240

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00194

Hom.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over