Variant 17-41502378-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153490.3(KRT13):c.1240G>A(p.Ala414Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KRT13
NM_153490.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.15

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13330802).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT13	NM_153490.3 link	c.1240G>A	p.Ala414Thr	missense_variant	6/8	ENST00000246635.8	NP_705694.3	P13646-1A1A4E9
KRT13	NM_002274.4 link	c.1240G>A	p.Ala414Thr	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 link	c.1240G>A	p.Ala414Thr	missense_variant	6/8	1	NM_153490.3	ENSP00000246635.3		P13646-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251398

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.1240G>A (p.A414T) alteration is located in exon 6 (coding exon 6) of the KRT13 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the alanine (A) at amino acid position 414 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.11

T;T;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.27

Sift

Benign

0.12

T;T;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.86

P;P;.

Vest4

0.15

MutPred

0.38

Gain of phosphorylation at A414 (P = 0.0626);Gain of phosphorylation at A414 (P = 0.0626);Gain of phosphorylation at A414 (P = 0.0626);

MVP

0.68

MPC

0.21

ClinPred

0.33

GERP RS

-0.32

Varity_R

0.10

gMVP

0.018

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

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