Variant 21-44592154-C-T 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_198688.3(KRTAP10-6):c.331G>A(p.Val111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,563,524 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

KRTAP10-6
NM_198688.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.337

Variant links:

Genes affected

KRTAP10-6 (HGNC:20523): (keratin associated protein 10-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-6 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=0.010167271).

BP6

Variant 21-44592154-C-T is Benign according to our data. Variant chr21-44592154-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652768.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-6	NM_198688.3 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	1/1	ENST00000400368.1
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-24149G>A		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-24149G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-6	ENST00000400368.1 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	1/1		NM_198688.3	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-24149G>A		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*28-24149G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000983

AC:

135

AN:

137348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000778

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000158

Gnomad OTH

AF:

0.00212

GnomAD3 exomes

AF:

0.000460

AC:

110

AN:

238972

Hom.:

AF XY:

0.000400

AC XY:

AN XY:

130034

show subpopulations

Gnomad AFR exome

AF:

0.00440

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000316

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.000215

AC:

306

AN:

1426062

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

153

AN XY:

709708

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.000321

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000710

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.000511

GnomAD4 genome

AF:

0.000982

AC:

135

AN:

137462

Hom.:

Cov.:

AF XY:

0.000871

AC XY:

AN XY:

66628

show subpopulations

Gnomad4 AFR

AF:

0.00311

Gnomad4 AMR

AF:

0.000777

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000158

Gnomad4 OTH

AF:

0.00210

Alfa

AF:

0.000590

Hom.:

ESP6500AA

AF:

0.00323

AC:

ESP6500EA

AF:

0.000475

AC:

ExAC

AF:

0.000460

AC:

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

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

KRTAP10-6: BP4, BS2; TSPEAR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

Cadd

Benign

9.7

Dann

Benign

0.84

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

M_CAP

Benign

0.0042

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.6

REVEL

Benign

0.017

Sift

Benign

0.075

Sift4G

Benign

0.11

Vest4

0.073

MVP

0.014

MPC

0.48

ClinPred

0.0092

GERP RS

-0.96

gMVP

0.060

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