NM_198693.4:c.259C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198693.4(KRTAP10-2):c.259C>T(p.Pro87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,585,220 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

KRTAP10-2
NM_198693.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.536

Publications

0 publications found

Variant links:

Genes affected

KRTAP10-2 (HGNC:22967): (keratin associated protein 10-2) This gene encodes a member of the high sulfur-type keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. This gene is located in a cluster of similar genes on 21q22.3. Alternatively-spliced transcript variants have been identified. [provided by RefSeq, Jan 2015]

KRTAP10-2 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048045576).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-2	NM_198693.4	MANE Select	c.259C>T	p.Pro87Ser	missense	Exon 1 of 1	NP_941966.1	P60368-1
TSPEAR	NM_144991.3	MANE Select	c.303+16585C>T		intron	N/A	NP_659428.2
TSPEAR	NM_001272037.2		c.99+16585C>T		intron	N/A	NP_001258966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP10-2	ENST00000391621.1	TSL:6 MANE Select	c.259C>T	p.Pro87Ser	missense	Exon 1 of 1	ENSP00000375479.1	P60368-1
TSPEAR	ENST00000323084.9	TSL:1 MANE Select	c.303+16585C>T		intron	N/A	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000397916.1	TSL:1	n.258+16585C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000600

AC:

AN:

250048

AF XY:

0.0000591

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000621

AC:

AN:

1433004

Hom.:

Cov.:

176

AF XY:

0.0000673

AC XY:

AN XY:

713682

show subpopulations

African (AFR)

AF:

0.0000617

AC:

AN:

32410

American (AMR)

AF:

0.0000448

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.000105

AC:

AN:

85774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52964

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000672

AC:

AN:

1086620

Other (OTH)

AF:

0.0000336

AC:

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

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:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000480

Hom.:

ExAC

AF:

0.0000907

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.085

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.13

M_CAP

Benign

0.0036

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

PhyloP100

0.54

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.12

Sift

Uncertain

0.024

Sift4G

Uncertain

0.060

Polyphen

0.025

Vest4

0.11

MVP

0.076

MPC

0.057

ClinPred

0.056

GERP RS

0.43

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.18

gMVP

0.067

Mutation Taster

=100/0

polymorphism

(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

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