Variant chr12-52469307-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_173086.5(KRT6C):c.1460-10C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,608 control chromosomes in the GnomAD database, including 40,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4295 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35716 hom. )

Consequence

KRT6C
NM_173086.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.003670

Clinical Significance

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

Conservation

PhyloP100: -0.986

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 (BayesDel_noAF=-0.8).

BP6

Variant 12-52469307-G-T is Benign according to our data. Variant chr12-52469307-G-T is described in ClinVar as [Benign]. Clinvar id is 1300091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 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.1460-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000252250.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT6C	ENST00000252250.7 linkuse as main transcript	c.1460-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_173086.5	P1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35688

AN:

152026

Hom.:

4283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.232

AC:

58207

AN:

250594

Hom.:

7060

AF XY:

0.228

AC XY:

30851

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.218

AC:

318726

AN:

1461464

Hom.:

35716

Cov.:

AF XY:

0.217

AC XY:

157695

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.235

AC:

35715

AN:

152144

Hom.:

4295

Cov.:

AF XY:

0.238

AC XY:

17717

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.220

Hom.:

1076

Bravo

AF:

0.238

Asia WGS

AF:

0.225

AC:

785

AN:

3478

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

Oct 23, 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 29, 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

-0.80

CADD

Benign

0.83

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0037

dbscSNV1_RF

Benign

0.17

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