17-41501347-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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:2

Conservation

PhyloP100: -0.591

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 323075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT13	NM_153490.3 linkuse as main transcript	c.1286G>A	p.Arg429His	missense_variant	8/8	ENST00000246635.8
KRT13	NM_002274.4 linkuse as main transcript	c.1260G>A	p.Pro420=	synonymous_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT13	ENST00000246635.8 linkuse as main transcript	c.1286G>A	p.Arg429His	missense_variant	8/8	1	NM_153490.3	P2	P13646-1
	ENST00000411759.1 linkuse as main transcript	n.334+31C>T		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.00174

AC:

302

AN:

173278

Hom.:

AF XY:

0.00164

AC XY:

150

AN XY:

91404

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 SAS exome

AF:

0.000381

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

Gnomad4 AFR exome

AF:

0.000488

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.0000793

Gnomad4 SAS exome

AF:

0.000275

Gnomad4 FIN exome

AF:

0.000360

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152230

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00219

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

KRT13: BP4, BS1, BS2 -

White sponge nevus 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

Cadd

Benign

5.1

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

MutationTaster

Benign

1.0

N;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over