Variant 21-44638127-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_181688.3(KRTAP10-10):c.710G>A(p.Arg237His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,612,976 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 27)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

KRTAP10-10
NM_181688.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005972475).

BP6

Variant 21-44638127-G-A is Benign according to our data. Variant chr21-44638127-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-10	NM_181688.3 linkuse as main transcript	c.710G>A	p.Arg237His	missense_variant	1/1	ENST00000380095.2
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-70122C>T		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+52418C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-10	ENST00000380095.2 linkuse as main transcript	c.710G>A	p.Arg237His	missense_variant	1/1		NM_181688.3	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-70122C>T		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*27+52418C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

402

AN:

151438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000790

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00115

AC:

286

AN:

249764

Hom.:

AF XY:

0.000903

AC XY:

122

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00580

Gnomad EAS exome

AF:

0.000715

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000480

AC:

701

AN:

1461420

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

314

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00962

Gnomad4 AMR exome

AF:

0.000940

Gnomad4 ASJ exome

AF:

0.00433

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00269

AC:

408

AN:

151556

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

184

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.00851

Gnomad4 AMR

AF:

0.000789

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.000835

Hom.:

Bravo

AF:

0.00308

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Jun 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.058

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.19

Polyphen

0.027

.;B

Vest4

0.11

MVP

0.16

MPC

0.069

ClinPred

0.024

GERP RS

1.5

Varity_R

0.076

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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