21-44539388-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_198691.3(KRTAP10-1):c.763G>A(p.Ala255Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,612,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

KRTAP10-1
NM_198691.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.76

Publications

0 publications found

Variant links:

Genes affected

KRTAP10-1 (HGNC:22966): (keratin associated protein 10-1) This gene encodes a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This gene encodes a member of the high sulfur KAP family. It is localized to a cluster of intronless KAPs at 21q22.3 which are located within the introns of the C21orf29 gene. [provided by RefSeq, Jul 2008]

KRTAP10-1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049251914).

BP6

Variant 21-44539388-C-T is Benign according to our data. Variant chr21-44539388-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2237503.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198691.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-1	NM_198691.3	MANE Select	c.763G>A	p.Ala255Thr	missense	Exon 1 of 1	NP_941964.2	P60331
TSPEAR	NM_144991.3	MANE Select	c.304-5465G>A		intron	N/A	NP_659428.2
TSPEAR	NM_001272037.2		c.100-5465G>A		intron	N/A	NP_001258966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-1	ENST00000400375.1	TSL:6 MANE Select	c.763G>A	p.Ala255Thr	missense	Exon 1 of 1	ENSP00000383226.1	P60331
TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.304-5465G>A		intron	N/A	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000397916.1	TSL:1	n.259-5465G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000273

AC:

AN:

249440

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000203

AC:

296

AN:

1460406

Hom.:

Cov.:

126

AF XY:

0.000184

AC XY:

134

AN XY:

726516

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33386

American (AMR)

AF:

0.000381

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26106

East Asian (EAS)

AF:

0.000984

AC:

AN:

39624

South Asian (SAS)

AF:

0.000244

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

0.000185

AC:

206

AN:

1111336

Other (OTH)

AF:

0.000166

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000197

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41450

American (AMR)

AF:

0.000131

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00213

AC:

AN:

5158

South Asian (SAS)

AF:

0.000209

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000104

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.016

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.0061

M_CAP

Benign

0.0010

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.045

PhyloP100

-1.8

PrimateAI

Benign

0.18

PROVEAN

Benign

1.5

REVEL

Benign

0.024

Sift

Benign

0.79

Sift4G

Benign

0.67

Polyphen

0.0010

Vest4

0.077

MVP

0.092

MPC

0.14

ClinPred

0.015

GERP RS

-5.8

Varity_R

0.023

gMVP

0.021

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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