Variant rs61029972 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000323084.9(TSPEAR):c.83-69712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 848,560 control chromosomes in the GnomAD database, including 1,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 627 hom., cov: 16)

Exomes 𝑓: 0.012 ( 669 hom. )

Consequence

TSPEAR
ENST00000323084.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0380

Variant links:

Genes affected

KRTAP10-10 (HGNC:22972): (keratin associated protein 10-10) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-10 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 21-44637717-T-C is Benign according to our data. Variant chr21-44637717-T-C is described in ClinVar as [Benign]. Clinvar id is 403022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRTAP10-10	NM_181688.3 linkuse as main transcript	c.300T>C	p.Cys100=	synonymous_variant	1/1	ENST00000380095.2	NP_859016.1
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-69712A>G		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+52828A>G		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-10	ENST00000380095.2 linkuse as main transcript	c.300T>C	p.Cys100=	synonymous_variant	1/1		NM_181688.3	ENSP00000369438	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-69712A>G		intron_variant		1	NM_144991.3	ENSP00000321987	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*27+52828A>G		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

7853

AN:

70116

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.00238

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.000739

Gnomad MID

AF:

0.116

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.0946

GnomAD3 exomes

AF:

0.0178

AC:

3724

AN:

208662

Hom.:

276

AF XY:

0.0135

AC XY:

1550

AN XY:

114674

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00687

Gnomad EAS exome

AF:

0.00301

Gnomad SAS exome

AF:

0.00776

Gnomad FIN exome

AF:

0.000273

Gnomad NFE exome

AF:

0.000956

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.0118

AC:

9156

AN:

778370

Hom.:

669

Cov.:

AF XY:

0.0106

AC XY:

4151

AN XY:

390226

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.0241

Gnomad4 ASJ exome

AF:

0.00928

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.000522

Gnomad4 NFE exome

AF:

0.000867

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.112

AC:

7891

AN:

70190

Hom.:

627

Cov.:

AF XY:

0.108

AC XY:

3683

AN XY:

34236

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.0180

Gnomad4 EAS

AF:

0.00239

Gnomad4 SAS

AF:

0.0190

Gnomad4 FIN

AF:

0.000739

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.0973

Alfa

AF:

0.155

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.0

DANN

Benign

0.33

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.

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