17-41502380-T-A

Position:

chr17-41502380-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_153490.3(KRT13):c.1238A>T(p.Asp413Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

KRT13
NM_153490.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.597

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:

ENSG00000229732 (HGNC:):

ENSG00000229732 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19326732).

BP6

Variant 17-41502380-T-A is Benign according to our data. Variant chr17-41502380-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 889824.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT13	NM_153490.3 linkuse as main transcript	c.1238A>T	p.Asp413Val	missense_variant	6/8	ENST00000246635.8	NP_705694.3	P13646-1A1A4E9
KRT13	NM_002274.4 linkuse as main transcript	c.1238A>T	p.Asp413Val	missense_variant	6/7		NP_002265.3	P13646-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT13	ENST00000246635.8 linkuse as main transcript	c.1238A>T	p.Asp413Val	missense_variant	6/8	1	NM_153490.3	ENSP00000246635.3		P13646-1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

251410

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461830

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

White sponge nevus 2

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

D;.;D

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.3

D;D;.

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.028

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.65

MutPred

0.73

Gain of methylation at K415 (P = 0.0365);Gain of methylation at K415 (P = 0.0365);Gain of methylation at K415 (P = 0.0365);

MVP

0.93

MPC

0.58

ClinPred

0.48

GERP RS

4.5

Varity_R

0.87

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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