21-44637719-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_181688.3(KRTAP10-10):c.302T>A(p.Val101Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,240,304 control chromosomes in the GnomAD database, including 1,277 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.059 ( 620 hom., cov: 29)

Exomes 𝑓: 0.0082 ( 657 hom. )

Consequence

KRTAP10-10
NM_181688.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021847188).

BP6

Variant 21-44637719-T-A is Benign according to our data. Variant chr21-44637719-T-A is described in ClinVar as [Benign]. Clinvar id is 377117.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-10	NM_181688.3 linkuse as main transcript	c.302T>A	p.Val101Glu	missense_variant	1/1	ENST00000380095.2
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-69714A>T		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+52826A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-10	ENST00000380095.2 linkuse as main transcript	c.302T>A	p.Val101Glu	missense_variant	1/1		NM_181688.3	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-69714A>T		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*27+52826A>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

7826

AN:

133960

Hom.:

610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.00802

Gnomad EAS

AF:

0.00125

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.000226

Gnomad MID

AF:

0.0403

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.0485

GnomAD3 exomes

AF:

0.0148

AC:

3692

AN:

250286

Hom.:

274

AF XY:

0.0113

AC XY:

1533

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.00917

Gnomad ASJ exome

AF:

0.00608

Gnomad EAS exome

AF:

0.00223

Gnomad SAS exome

AF:

0.00706

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000741

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00820

AC:

9066

AN:

1106236

Hom.:

657

Cov.:

110

AF XY:

0.00751

AC XY:

4109

AN XY:

547334

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.00669

Gnomad4 EAS exome

AF:

0.00168

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.000355

Gnomad4 NFE exome

AF:

0.000528

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0587

AC:

7864

AN:

134068

Hom.:

620

Cov.:

AF XY:

0.0564

AC XY:

3671

AN XY:

65138

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.0251

Gnomad4 ASJ

AF:

0.00802

Gnomad4 EAS

AF:

0.00125

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.000226

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.00634

Hom.:

Bravo

AF:

0.0609

ESP6500AA

AF:

0.125

AC:

550

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0202

AC:

2186

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jun 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

Cadd

Benign

5.6

Dann

Benign

0.42

DEOGEN2

Benign

0.0043

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.038

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

2.3

REVEL

Benign

0.012

Sift

Benign

0.23

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.19

MPC

0.073

ClinPred

0.0014

GERP RS

-5.7

Varity_R

0.085

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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