Variant 12-52469429-C-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_173086.5(KRT6C):c.1441G>A(p.Val481Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,613,648 control chromosomes in the GnomAD database, including 99,628 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6890 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92738 hom. )

Consequence

KRT6C
NM_173086.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.928

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025770068).

BP6

Variant 12-52469429-C-T is Benign according to our data. Variant chr12-52469429-C-T is described in ClinVar as [Benign]. Clinvar id is 1300092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT6C	NM_173086.5 linkuse as main transcript	c.1441G>A	p.Val481Ile	missense_variant	8/9	ENST00000252250.7	NP_775109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT6C	ENST00000252250.7 linkuse as main transcript	c.1441G>A	p.Val481Ile	missense_variant	8/9	1	NM_173086.5	ENSP00000252250	P1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40704

AN:

151946

Hom.:

6886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.321

AC:

80497

AN:

251090

Hom.:

14164

AF XY:

0.321

AC XY:

43623

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0609

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.349

AC:

509666

AN:

1461584

Hom.:

92738

Cov.:

AF XY:

0.346

AC XY:

251476

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0551

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.268

AC:

40703

AN:

152064

Hom.:

6890

Cov.:

AF XY:

0.266

AC XY:

19761

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0703

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.332

Hom.:

3014

Bravo

AF:

0.263

TwinsUK

AF:

0.377

AC:

1398

ALSPAC

AF:

0.362

AC:

1397

ESP6500AA

AF:

0.0717

AC:

316

ESP6500EA

AF:

0.368

AC:

3163

ExAC

AF:

0.315

AC:

38248

EpiCase

AF:

0.358

EpiControl

AF:

0.359

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KRT6C-related disorder

Benign:1

Benign, no assertion criteria provided

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). -

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

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.98

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.78

REVEL

Benign

0.27

Sift

Benign

0.21

Sift4G

Benign

0.46

Polyphen

0.82

Vest4

0.063

MPC

0.13

ClinPred

0.013

GERP RS

3.6

Varity_R

0.094

gMVP

0.58

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