rs200384147

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198689.3(KRTAP10-7):c.46G>A(p.Gly16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,612,514 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 112 hom. )

Consequence

KRTAP10-7
NM_198689.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.361

Publications

5 publications found

Variant links:

Genes affected

KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 98
Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002353847).

BP6

Variant 21-44600667-G-A is Benign according to our data. Variant chr21-44600667-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 377277.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00413 (626/151652) while in subpopulation SAS AF = 0.0447 (214/4792). AF 95% confidence interval is 0.0398. There are 11 homozygotes in GnomAd4. There are 355 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP10-7	NM_198689.3 link	c.46G>A	p.Gly16Ser	missense_variant	Exon 1 of 1	ENST00000609664.2	NP_941962.1	P60409
TSPEAR	NM_144991.3 link	c.83-32662C>T		intron_variant	Intron 1 of 11	ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 link	c.-122-32662C>T		intron_variant	Intron 2 of 12		NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRTAP10-7	ENST00000609664.2 link	c.46G>A	p.Gly16Ser	missense_variant	Exon 1 of 1	6	NM_198689.3	ENSP00000476821.1	P60409
TSPEAR	ENST00000323084.9 link	c.83-32662C>T		intron_variant	Intron 1 of 11	1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 link	n.*28-32662C>T		intron_variant	Intron 2 of 12			ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

629

AN:

151536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00831

Gnomad SAS

AF:

0.0450

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00529

GnomAD2 exomes

AF:

0.00776

AC:

1913

AN:

246598

AF XY:

0.00932

show subpopulations

Gnomad AFR exome

AF:

0.00311

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00728

Gnomad EAS exome

AF:

0.00736

Gnomad FIN exome

AF:

0.000518

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.00444

AC:

6484

AN:

1460862

Hom.:

112

Cov.:

AF XY:

0.00545

AC XY:

3959

AN XY:

726622

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00330

AC:

110

AN:

33306

American (AMR)

AF:

0.00116

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00698

AC:

182

AN:

26074

East Asian (EAS)

AF:

0.00763

AC:

303

AN:

39692

South Asian (SAS)

AF:

0.0399

AC:

3429

AN:

85984

European-Finnish (FIN)

AF:

0.000732

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00180

AC:

2006

AN:

1111798

Other (OTH)

AF:

0.00574

AC:

346

AN:

60316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.386

Heterozygous variant carriers

415

830

1245

1660

2075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00413

AC:

626

AN:

151652

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

355

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.00385

AC:

158

AN:

41046

American (AMR)

AF:

0.00164

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

AN:

3468

East Asian (EAS)

AF:

0.00814

AC:

AN:

5162

South Asian (SAS)

AF:

0.0447

AC:

214

AN:

4792

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00213

AC:

145

AN:

67984

Other (OTH)

AF:

0.00523

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00326

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00178

AC:

ExAC

AF:

0.00862

AC:

1038

EpiCase

AF:

0.00240

EpiControl

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.5

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.068

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PhyloP100

-0.36

PrimateAI

Benign

0.24

Sift4G

Benign

0.27

Vest4

0.19

MVP

0.24

ClinPred

0.00061

GERP RS

-3.3

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.027

gMVP

0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over