Variant 21-44551193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198693.4(KRTAP10-2):c.266G>A(p.Cys89Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP10-2
NM_198693.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

KRTAP10-2 (HGNC:22967): (keratin associated protein 10-2) This gene encodes a member of the high sulfur-type keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. This gene is located in a cluster of similar genes on 21q22.3. Alternatively-spliced transcript variants have been identified. [provided by RefSeq, Jan 2015]

KRTAP10-2 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:

TSPEAR (HGNC:):

TSPEAR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-2	NM_198693.4 linkuse as main transcript	c.266G>A	p.Cys89Tyr	missense_variant	1/1	ENST00000391621.1	NP_941966.1	P60368-1
TSPEAR	NM_144991.3 linkuse as main transcript	c.303+16592G>A		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.99+16592G>A		intron_variant			NP_001258966.1	Q8WU66
KRTAP10-2	NR_130165.2 linkuse as main transcript	n.126+187G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-2	ENST00000391621.1 linkuse as main transcript	c.266G>A	p.Cys89Tyr	missense_variant	1/1	6	NM_198693.4	ENSP00000375479.1		P60368-1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.303+16592G>A		intron_variant		1	NM_144991.3	ENSP00000321987.4		Q8WU66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250052

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000487

AC:

AN:

1437506

Hom.:

Cov.:

178

AF XY:

0.00000279

AC XY:

AN XY:

715632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000642

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.266G>A (p.C89Y) alteration is located in exon 1 (coding exon 1) of the KRTAP10-2 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the cysteine (C) at amino acid position 89 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.33

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.23

M_CAP

Benign

0.0081

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-11

REVEL

Benign

0.17

Sift

Uncertain

0.016

Sift4G

Uncertain

0.012

Polyphen

0.025

Vest4

0.16

MVP

0.10

MPC

0.089

ClinPred

0.70

GERP RS

2.9

Varity_R

0.55

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.33

Position offset: -23

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