Variant 12-52469254-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173086.5(KRT6C):c.1503C>T(p.Ser501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,613,266 control chromosomes in the GnomAD database, including 99,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6898 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92723 hom. )

Consequence

KRT6C
NM_173086.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.578

Variant links:

Genes affected

KRT6C (HGNC:20406): (keratin 6C) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. The type II keratins are clustered in a region of chromosome 12q13. [provided by RefSeq, Jul 2009]

KRT6C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-52469254-G-A is Benign according to our data. Variant chr12-52469254-G-A is described in ClinVar as [Benign]. Clinvar id is 1300090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.578 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT6C	NM_173086.5 linkuse as main transcript	c.1503C>T	p.Ser501=	synonymous_variant	9/9	ENST00000252250.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT6C	ENST00000252250.7 linkuse as main transcript	c.1503C>T	p.Ser501=	synonymous_variant	9/9	1	NM_173086.5	P1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40729

AN:

151984

Hom.:

6894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.320

AC:

79853

AN:

249798

Hom.:

13927

AF XY:

0.321

AC XY:

43313

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.0607

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.487

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.349

AC:

509627

AN:

1461164

Hom.:

92723

Cov.:

AF XY:

0.346

AC XY:

251468

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.300

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.268

AC:

40728

AN:

152102

Hom.:

6898

Cov.:

AF XY:

0.266

AC XY:

19775

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.291

Alfa

AF:

0.292

Hom.:

3146

Bravo

AF:

0.263

Asia WGS

AF:

0.295

AC:

1027

AN:

3478

EpiCase

AF:

0.358

EpiControl

AF:

0.358

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

KRT6C-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Palmoplantar keratoderma, nonepidermolytic, focal or diffuse

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.059

DANN

Benign

0.64

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