Genetic Variant KRTAP10-11:p.Pro39Pro (chr21-44646575-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_198692.3(KRTAP10-11):c.117G>A(p.Pro39Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,612,200 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

KRTAP10-11
NM_198692.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.41

Variant links:

Genes affected

KRTAP10-11 (HGNC:20528): (keratin associated protein 10-11) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-11 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-4.41 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP10-11	NM_198692.3 link	c.117G>A	p.Pro39Pro	synonymous_variant	Exon 1 of 1	ENST00000334670.9	NP_941965.2	P60411P60412
TSPEAR	NM_144991.3 link	c.82+64858C>T		intron_variant	Intron 1 of 11	ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 link	c.-123+43970C>T		intron_variant	Intron 2 of 12		NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRTAP10-11	ENST00000334670.9 link	c.117G>A	p.Pro39Pro	synonymous_variant	Exon 1 of 1	6	NM_198692.3	ENSP00000334197.8	P60412
TSPEAR	ENST00000323084.9 link	c.82+64858C>T		intron_variant	Intron 1 of 11	1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 link	n.*27+43970C>T		intron_variant	Intron 2 of 12			ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00231

AC:

574

AN:

248064

Hom.:

AF XY:

0.00229

AC XY:

309

AN XY:

134762

show subpopulations

Gnomad AFR exome

AF:

0.000528

Gnomad AMR exome

AF:

0.000812

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.000831

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00270

AC:

3942

AN:

1460072

Hom.:

Cov.:

151

AF XY:

0.00264

AC XY:

1916

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.000956

Gnomad4 NFE exome

AF:

0.00292

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00221

AC:

336

AN:

152128

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KRTAP10-11: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.56

DANN

Benign

0.64

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