rs143765249

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_181688.3(KRTAP10-10):c.710G>A(p.Arg237His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,612,976 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 27)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

KRTAP10-10
NM_181688.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 98
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

TSPEAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005972475).

BP6

Variant 21-44638127-G-A is Benign according to our data. Variant chr21-44638127-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 377299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181688.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-10	NM_181688.3	MANE Select	c.710G>A	p.Arg237His	missense	Exon 1 of 1	NP_859016.1	P60014
TSPEAR	NM_144991.3	MANE Select	c.83-70122C>T		intron	N/A	NP_659428.2
TSPEAR	NM_001272037.2		c.-123+52418C>T		intron	N/A	NP_001258966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-10	ENST00000380095.2	TSL:6 MANE Select	c.710G>A	p.Arg237His	missense	Exon 1 of 1	ENSP00000369438.1	P60014
TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.83-70122C>T		intron	N/A	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000943283.1		c.83-70122C>T		intron	N/A	ENSP00000613342.1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

402

AN:

151438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000790

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00337

GnomAD2 exomes

AF:

0.00115

AC:

286

AN:

249764

AF XY:

0.000903

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00580

Gnomad EAS exome

AF:

0.000715

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000480

AC:

701

AN:

1461420

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

314

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.00962

AC:

322

AN:

33476

American (AMR)

AF:

0.000940

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

113

AN:

26086

East Asian (EAS)

AF:

0.000403

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000111

AC:

123

AN:

1111788

Other (OTH)

AF:

0.00113

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00269

AC:

408

AN:

151556

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

184

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.00851

AC:

352

AN:

41362

American (AMR)

AF:

0.000789

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67804

Other (OTH)

AF:

0.00333

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000835

Hom.:

Bravo

AF:

0.00308

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.058

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

PhyloP100

-0.013

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.063

Sift

Benign

0.042

Sift4G

Benign

0.087

Polyphen

0.027

Vest4

0.11

MVP

0.16

MPC

0.069

ClinPred

0.024

GERP RS

1.5

Varity_R

0.076

gMVP

0.047

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over