Variant chr21-44600667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000323084.9(TSPEAR):c.83-32662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,612,514 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 112 hom. )

Consequence

TSPEAR
ENST00000323084.9 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.361

Variant links:

Genes affected

KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-7 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002353847).

BP6

Variant 21-44600667-G-A is Benign according to our data. Variant chr21-44600667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377277.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00413 (626/151652) while in subpopulation SAS AF= 0.0447 (214/4792). AF 95% confidence interval is 0.0398. There are 11 homozygotes in gnomad4. There are 355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-7	NM_198689.3 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	1/1	ENST00000609664.2	NP_941962.1	P60409
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-32662C>T		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-32662C>T		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP10-7	ENST00000609664.2 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	1/1	6	NM_198689.3	ENSP00000476821.1	P60409
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-32662C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*28-32662C>T		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

629

AN:

151536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00831

Gnomad SAS

AF:

0.0450

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00529

GnomAD3 exomes

AF:

0.00776

AC:

1913

AN:

246598

Hom.:

AF XY:

0.00932

AC XY:

1250

AN XY:

134134

show subpopulations

Gnomad AFR exome

AF:

0.00311

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00728

Gnomad EAS exome

AF:

0.00736

Gnomad SAS exome

AF:

0.0442

Gnomad FIN exome

AF:

0.000518

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.00444

AC:

6484

AN:

1460862

Hom.:

112

Cov.:

AF XY:

0.00545

AC XY:

3959

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.00330

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00698

Gnomad4 EAS exome

AF:

0.00763

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.000732

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00574

GnomAD4 genome

AF:

0.00413

AC:

626

AN:

151652

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

355

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00814

Gnomad4 SAS

AF:

0.0447

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00523

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00326

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00178

AC:

ExAC

AF:

0.00862

AC:

1038

EpiCase

AF:

0.00240

EpiControl

AF:

0.00237

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

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.5

DANN

Benign

0.79

DEOGEN2

Benign

0.068

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

Sift4G

Benign

0.27

Vest4

0.19

MVP

0.24

ClinPred

0.00061

GERP RS

-3.3

Varity_R

0.027

gMVP

0.064

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