Variant 21-44637579-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181688.3(KRTAP10-10):c.162G>T(p.Gln54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

KRTAP10-10
NM_181688.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.95

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13068497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-10	NM_181688.3 linkuse as main transcript	c.162G>T	p.Gln54His	missense_variant	1/1	ENST00000380095.2	NP_859016.1	P60014
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-69574C>A		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+52966C>A		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP10-10	ENST00000380095.2 linkuse as main transcript	c.162G>T	p.Gln54His	missense_variant	1/1	6	NM_181688.3	ENSP00000369438.1	P60014
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-69574C>A		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*27+52966C>A		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251252

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461568

Hom.:

Cov.:

131

AF XY:

0.0000289

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000576

AC:

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

Oct 20, 2021

The c.162G>T (p.Q54H) alteration is located in exon 1 (coding exon 1) of the KRTAP10-10 gene. This alteration results from a G to T substitution at nucleotide position 162, causing the glutamine (Q) at amino acid position 54 to be replaced by a histidine (H). 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

0.27

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.055

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0037

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.12

Sift

Uncertain

0.013

Sift4G

Uncertain

0.0070

Polyphen

0.97

Vest4

0.22

MutPred

0.40

Gain of catalytic residue at Q54 (P = 0.1362);

MVP

0.072

MPC

0.046

ClinPred

0.48

GERP RS

1.1

Varity_R

0.13

gMVP

0.088

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