Variant chr12-52469144-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173086.5(KRT6C):c.1613G>C(p.Gly538Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,614,032 control chromosomes in the GnomAD database, including 781 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 35 hom., cov: 32)

Exomes 𝑓: 0.029 ( 746 hom. )

Consequence

KRT6C
NM_173086.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.82

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037206411).

BP6

Variant 12-52469144-C-G is Benign according to our data. Variant chr12-52469144-C-G is described in ClinVar as [Benign]. Clinvar id is 1600014.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2915/152316) while in subpopulation NFE AF= 0.0306 (2083/68016). AF 95% confidence interval is 0.0295. There are 35 homozygotes in gnomad4. There are 1307 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2915 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT6C	NM_173086.5 linkuse as main transcript	c.1613G>C	p.Gly538Ala	missense_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.1613G>C	p.Gly538Ala	missense_variant	9/9	1	NM_173086.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2914

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0204

AC:

5128

AN:

251350

Hom.:

AF XY:

0.0207

AC XY:

2811

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0306

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00983

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0305

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0293

AC:

42764

AN:

1461716

Hom.:

746

Cov.:

AF XY:

0.0287

AC XY:

20903

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00999

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.0340

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0191

AC:

2915

AN:

152316

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1307

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00558

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0289

Hom.:

Bravo

AF:

0.0195

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.0348

AC:

299

ExAC

AF:

0.0195

AC:

2365

EpiCase

AF:

0.0311

EpiControl

AF:

0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.037

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.34

Sift

Benign

0.28

Sift4G

Uncertain

0.035

Polyphen

0.54

Vest4

0.085

MPC

0.18

ClinPred

0.019

GERP RS

2.6

Varity_R

0.11

gMVP

0.59

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