Genetic Variant KRT13:p.Arg451Leu (chr17-41501281-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153490.3(KRT13):c.1352G>T(p.Arg451Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R451H) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT13
NM_153490.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22493204).

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.1352G>T	p.Arg451Leu	missense	Exon 8 of 8	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.*63G>T		3_prime_UTR	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.1352G>T	p.Arg451Leu	missense	Exon 8 of 8	ENSP00000246635.3	P13646-1
KRT13	ENST00000336861.7	TSL:1	c.*63G>T		3_prime_UTR	Exon 7 of 7	ENSP00000336604.3	P13646-3
KRT13	ENST00000970738.1		c.1349G>T	p.Arg450Leu	missense	Exon 8 of 8	ENSP00000640797.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700684

African (AFR)

AF:

0.00

AC:

AN:

32958

American (AMR)

AF:

0.00

AC:

AN:

37042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25274

East Asian (EAS)

AF:

0.00

AC:

AN:

38148

South Asian (SAS)

AF:

0.00

AC:

AN:

80430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088886

Other (OTH)

AF:

0.00

AC:

AN:

58862

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.55

M_CAP

Benign

0.054

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Benign

0.35

PROVEAN

Benign

0.62

REVEL

Uncertain

0.33

Sift

Benign

0.067

Sift4G

Benign

0.40

Polyphen

0.96

Vest4

0.32

MutPred

0.28

Loss of sheet (P = 0.0457)

MVP

0.83

MPC

0.11

ClinPred

0.29

GERP RS

2.3

Varity_R

0.11

gMVP

0.082

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over