Variant 12-52519122-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000424.4(KRT5):c.594C>A(p.Thr198Thr) variant causes a synonymous change. The variant allele was found at a frequency of 0.261 in 1,610,090 control chromosomes in the GnomAD database, including 55,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4483 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51413 hom. )

Consequence

KRT5
NM_000424.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 4.53

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:

KRT5 (HGNC:):

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 (BayesDel_noAF=-0.57).

BP6

Variant 12-52519122-G-T is Benign according to our data. Variant chr12-52519122-G-T is described in ClinVar as [Benign]. Clinvar id is 66277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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.594C>A	p.Thr198Thr	synonymous_variant	2/9	ENST00000252242.9	NP_000415.2	P13647

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT5	ENST00000252242.9 linkuse as main transcript	c.594C>A	p.Thr198Thr	synonymous_variant	2/9	1	NM_000424.4	ENSP00000252242.4		P13647

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34896

AN:

151900

Hom.:

4483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.247

AC:

60894

AN:

246716

Hom.:

7536

AF XY:

0.246

AC XY:

32828

AN XY:

133460

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.265

AC:

386031

AN:

1458072

Hom.:

51413

Cov.:

AF XY:

0.263

AC XY:

190846

AN XY:

725528

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.271

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.230

AC:

34894

AN:

152018

Hom.:

4483

Cov.:

AF XY:

0.226

AC XY:

16809

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.357

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.248

Hom.:

2119

Bravo

AF:

0.231

Asia WGS

AF:

0.234

AC:

814

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

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

Epidermolysis bullosa simplex 1A, generalized severe;C0432316:Epidermolysis bullosa simplex with mottled pigmentation;C1836284:Epidermolysis bullosa simplex with migratory circinate erythema;C4552092:Dowling-Degos disease 1;C5562009:Epidermolysis bullosa simplex 2B, generalized intermediate;C5562011:Epidermolysis bullosa simplex 2C, localized;C5562014:Epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive;CN301077:Epidermolysis bullosa simplex 2A, generalized severe

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.69

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