Variant 17-41583245-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5

The NM_000526.5(KRT14):c.1264G>A(p.Glu422Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KRT14
NM_000526.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 links:

KRT14 (HGNC:):

KRT14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a region_of_interest Coil 2 (size 138) in uniprot entity K1C14_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_000526.5

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

PP5

Variant 17-41583245-C-T is Pathogenic according to our data. Variant chr17-41583245-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 14623.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 linkuse as main transcript	c.1264G>A	p.Glu422Lys	missense_variant	6/8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRT14	ENST00000167586.7 linkuse as main transcript	c.1264G>A	p.Glu422Lys	missense_variant	6/8	1	NM_000526.5	ENSP00000167586.6	P02533
KRT14	ENST00000441550.2 linkuse as main transcript	n.211G>A		non_coding_transcript_exon_variant	1/2	2
KRT14	ENST00000476662.1 linkuse as main transcript	n.*4G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251194

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135842

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461230

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726908

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Epidermolysis bullosa simplex 1C, localized

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2000

- -

not provided

Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.92

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.97

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

4.2

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.8

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.98

Vest4

0.92

MutPred

0.83

Gain of ubiquitination at E422 (P = 0.0054);

MVP

0.97

MPC

1.3

ClinPred

1.0

GERP RS

5.7

Varity_R

0.83

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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