Variant chr21-44612494-G-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_198695.2(KRTAP10-8):c.394G>T(p.Val132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,610,706 control chromosomes in the GnomAD database, including 83 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 0.0060 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 77 hom. )

Consequence

KRTAP10-8
NM_198695.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.747

Variant links:

Genes affected

KRTAP10-8 (HGNC:20525): (keratin associated protein 10-8) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-8 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012473196).

BP6

Variant 21-44612494-G-T is Benign according to our data. Variant chr21-44612494-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2571149.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-8	NM_198695.2 linkuse as main transcript	c.394G>T	p.Val132Leu	missense_variant	1/1	ENST00000334662.2	NP_941968.2	P60410
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-44489C>A		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-44489C>A		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP10-8	ENST00000334662.2 linkuse as main transcript	c.394G>T	p.Val132Leu	missense_variant	1/1	6	NM_198695.2	ENSP00000335565.2	P60410
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-44489C>A		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*28-44489C>A		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

905

AN:

150932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00149

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00789

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00387

GnomAD3 exomes

AF:

0.00557

AC:

1399

AN:

251282

Hom.:

AF XY:

0.00554

AC XY:

753

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00620

Gnomad NFE exome

AF:

0.00957

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00883

AC:

12887

AN:

1459658

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

6198

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00496

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00659

GnomAD4 genome

AF:

0.00599

AC:

905

AN:

151048

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

413

AN XY:

73764

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00270

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00789

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00383

Alfa

AF:

0.00856

Hom.:

Bravo

AF:

0.00560

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00533

AC:

647

EpiCase

AF:

0.00856

EpiControl

AF:

0.00883

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

Apr 01, 2023

KRTAP10-8: BP4, BS2; TSPEAR: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.69

DANN

Benign

0.87

DEOGEN2

Benign

0.080

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.18

M_CAP

Benign

0.0015

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.014

Sift

Uncertain

0.022

Sift4G

Benign

0.14

Polyphen

0.029

Vest4

0.061

MutPred

0.39

Loss of sheet (P = 0.1158);

MVP

0.20

MPC

0.062

ClinPred

0.0043

GERP RS

0.97

Varity_R

0.096

gMVP

0.056

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