chr12-52519884-C-T

Position:

chr12-52519884-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000424.4(KRT5):c.413G>A(p.Gly138Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0691 in 1,613,822 control chromosomes in the GnomAD database, including 4,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 300 hom., cov: 31)

Exomes 𝑓: 0.071 ( 4099 hom. )

Consequence

KRT5
NM_000424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 5.33

Variant links:

Genes affected

KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046600103).

BP6

Variant 12-52519884-C-T is Benign according to our data. Variant chr12-52519884-C-T is described in ClinVar as [Benign]. Clinvar id is 66234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-52519884-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT5	NM_000424.4 linkuse as main transcript	c.413G>A	p.Gly138Glu	missense_variant	1/9	ENST00000252242.9	NP_000415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT5	ENST00000252242.9 linkuse as main transcript	c.413G>A	p.Gly138Glu	missense_variant	1/9	1	NM_000424.4	ENSP00000252242	P1

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7939

AN:

151822

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0471

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.0898

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.0431

GnomAD3 exomes

AF:

0.0565

AC:

14213

AN:

251454

Hom.:

553

AF XY:

0.0585

AC XY:

7955

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.0979

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0552

GnomAD4 exome

AF:

0.0709

AC:

103650

AN:

1461882

Hom.:

4099

Cov.:

AF XY:

0.0706

AC XY:

51365

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0524

Gnomad4 FIN exome

AF:

0.0974

Gnomad4 NFE exome

AF:

0.0785

Gnomad4 OTH exome

AF:

0.0637

GnomAD4 genome

AF:

0.0523

AC:

7945

AN:

151940

Hom.:

300

Cov.:

AF XY:

0.0512

AC XY:

3802

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.0471

Gnomad4 EAS

AF:

0.000970

Gnomad4 SAS

AF:

0.0544

Gnomad4 FIN

AF:

0.0898

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.0427

Alfa

AF:

0.0696

Hom.:

1074

Bravo

AF:

0.0437

TwinsUK

AF:

0.0823

AC:

305

ALSPAC

AF:

0.0802

AC:

309

ESP6500AA

AF:

0.0161

AC:

ESP6500EA

AF:

0.0743

AC:

639

ExAC

AF:

0.0582

AC:

7061

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0762

EpiControl

AF:

0.0742

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 32885477, 17549391, 27884173, 20981092, 19578363, 20849457, 23746086) -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epidermolysis bullosa simplex

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Uncertain

0.0020

MutationAssessor

Pathogenic

3.6

H;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.2

D;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.0080

D;.;D

Polyphen

0.96

D;.;.

Vest4

0.35

MPC

0.95

ClinPred

0.095

GERP RS

5.5

Varity_R

0.82

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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