NM_153490.3:c.1286G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153490.3(KRT13):c.1286G>A(p.Arg429His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,564,846 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

KRT13
NM_153490.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.591

Publications

4 publications found

Variant links:

Genes affected

KRT13 (HGNC:6415): (keratin 13) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This type I cytokeratin is paired with keratin 4 and expressed in the suprabasal layers of non-cornified stratified epithelia. Mutations in this gene and keratin 4 have been associated with the autosomal dominant disorder White Sponge Nevus. The type I cytokeratins are clustered in a region of chromosome 17q21.2. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been described. [provided by RefSeq, Jul 2008]

KRT13 Gene-Disease associations (from GenCC):

white sponge nevus 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary mucosal leukokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT13 links:

ENSG00000229732 (HGNC:):

ENSG00000229732 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039369464).

BP6

Variant 17-41501347-C-T is Benign according to our data. Variant chr17-41501347-C-T is described in ClinVar as Benign. ClinVar VariationId is 323075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 235 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT13	NM_153490.3	MANE Select	c.1286G>A	p.Arg429His	missense	Exon 8 of 8	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.1260G>A	p.Pro420Pro	synonymous	Exon 7 of 7	NP_002265.3	P13646-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT13	ENST00000246635.8	TSL:1 MANE Select	c.1286G>A	p.Arg429His	missense	Exon 8 of 8	ENSP00000246635.3	P13646-1
KRT13	ENST00000336861.7	TSL:1	c.1260G>A	p.Pro420Pro	synonymous	Exon 7 of 7	ENSP00000336604.3	P13646-3
KRT13	ENST00000970738.1		c.1283G>A	p.Arg428His	missense	Exon 8 of 8	ENSP00000640797.1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

235

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00174

AC:

302

AN:

173278

AF XY:

0.00164

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.00209

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.000150

Gnomad FIN exome

AF:

0.000251

Gnomad NFE exome

AF:

0.00218

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00180

AC:

2537

AN:

1412616

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1262

AN XY:

697724

show subpopulations

African (AFR)

AF:

0.000488

AC:

AN:

32792

American (AMR)

AF:

0.00242

AC:

AN:

36420

Ashkenazi Jewish (ASJ)

AF:

0.00563

AC:

142

AN:

25214

East Asian (EAS)

AF:

0.0000793

AC:

AN:

37842

South Asian (SAS)

AF:

0.000275

AC:

AN:

80090

European-Finnish (FIN)

AF:

0.000360

AC:

AN:

50064

Middle Eastern (MID)

AF:

0.00385

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00191

AC:

2072

AN:

1085806

Other (OTH)

AF:

0.00262

AC:

154

AN:

58678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

116

232

347

463

579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00154

AC:

235

AN:

152230

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41550

American (AMR)

AF:

0.00235

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68008

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00222

Hom.:

Bravo

AF:

0.00168

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00119

AC:

135

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

White sponge nevus 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.1

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.38

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.86

PhyloP100

-0.59

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.65

REVEL

Benign

0.096

Sift

Benign

0.056

Sift4G

Benign

0.081

Polyphen

0.27

Vest4

0.058

MVP

0.61

MPC

0.12

ClinPred

0.0066

GERP RS

-4.8

Varity_R

0.025

gMVP

0.038

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

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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