chr21-44627283-G-A

Position:

chr21-44627283-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198690.3(KRTAP10-9):c.112G>A(p.Ala38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,612,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KRTAP10-9
NM_198690.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

KRTAP10-9 (HGNC:22971): (keratin associated protein 10-9) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-9 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:

KRTAP10-9 (HGNC:):

KRTAP10-9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06546959).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-9	NM_198690.3 linkuse as main transcript	c.112G>A	p.Ala38Thr	missense_variant	1/1	ENST00000397911.5	NP_941963.2	P60411-1
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-59278C>T		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-59278C>T		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP10-9	ENST00000397911.5 linkuse as main transcript	c.112G>A	p.Ala38Thr	missense_variant	1/1	6	NM_198690.3	ENSP00000381009.3	P60411-1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-59278C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
KRTAP10-9	ENST00000484861.1 linkuse as main transcript	n.161G>A		non_coding_transcript_exon_variant	1/2	1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*28-59278C>T		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000235

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000105

AC:

AN:

248634

Hom.:

AF XY:

0.0000667

AC XY:

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

168

AN:

1460230

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000112

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000351

AC:

ExAC

AF:

0.0000743

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Sep 12, 2024

The c.112G>A (p.A38T) alteration is located in exon 1 (coding exon 1) of the KRTAP10-9 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the alanine (A) at amino acid position 38 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.0

DANN

Benign

0.71

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.0069

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.70

N;.

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.022

Sift

Benign

0.13

T;.

Sift4G

Benign

0.54

T;T

Polyphen

0.20

B;.

Vest4

0.063

MVP

0.085

ClinPred

0.019

GERP RS

-3.5

Varity_R

0.047

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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