dbSNP rs200116408: TSPEAR:c.542+14C>T (chr21-44533671-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_144991.3(TSPEAR):c.542+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,595,716 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00097 ( 2 hom. )

Consequence

TSPEAR
NM_144991.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.66

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 98
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

TSPEAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-44533671-G-A is Benign according to our data. Variant chr21-44533671-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144991.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPEAR	NM_144991.3	MANE Select	c.542+14C>T		intron	N/A	NP_659428.2
	TSPEAR	NM_001272037.2		c.338+14C>T		intron	N/A	NP_001258966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.542+14C>T	intron	N/A	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000397916.1	TSL:1	n.497+14C>T	intron	N/A
TSPEAR	ENST00000943283.1		c.542+14C>T	intron	N/A	ENSP00000613342.1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000788

AC:

186

AN:

236136

AF XY:

0.000701

show subpopulations

Gnomad AFR exome

AF:

0.00330

Gnomad AMR exome

AF:

0.000645

Gnomad ASJ exome

AF:

0.000827

Gnomad EAS exome

AF:

0.0000554

Gnomad FIN exome

AF:

0.000109

Gnomad NFE exome

AF:

0.000960

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000969

AC:

1398

AN:

1443400

Hom.:

Cov.:

AF XY:

0.000909

AC XY:

651

AN XY:

716034

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

33192

American (AMR)

AF:

0.000676

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.000849

AC:

AN:

25910

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39346

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85682

European-Finnish (FIN)

AF:

0.000143

AC:

AN:

49118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5262

European-Non Finnish (NFE)

AF:

0.00110

AC:

1215

AN:

1100986

Other (OTH)

AF:

0.000873

AC:

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152316

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00315

AC:

131

AN:

41568

American (AMR)

AF:

0.000392

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68034

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000539

Hom.:

Bravo

AF:

0.00138

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.69

(source)

DANN

Benign

0.36

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over