Variant 12-52897540-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_002273.4(KRT8):c.1340C>T(p.Ala447Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 152,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT8
NM_002273.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

KRT8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022991091).

BP6

Variant 12-52897540-G-A is Benign according to our data. Variant chr12-52897540-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 56169.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT8	NM_002273.4 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	8/8	ENST00000692008.1	NP_002264.1
KRT8	NM_001256282.2 linkuse as main transcript	c.1424C>T	p.Ala475Val	missense_variant	9/9		NP_001243211.1
KRT8	NM_001256293.2 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	9/9		NP_001243222.1
KRT8	NR_045962.2 linkuse as main transcript	n.1791C>T		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000692008.1 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	8/8		NM_002273.4	ENSP00000509398	P2	P05787-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000192

AC:

AN:

234460

Hom.:

AF XY:

0.000195

AC XY:

AN XY:

128460

show subpopulations

Gnomad AFR exome

AF:

0.000202

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00160

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000827

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000531

AC:

AN:

1411850

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

704246

show subpopulations

Gnomad4 AFR exome

AF:

0.000274

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000608

Gnomad4 SAS exome

AF:

0.0000937

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000287

Gnomad4 OTH exome

AF:

0.0000508

GnomAD4 genome

AF:

0.000184

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00120

AC:

ESP6500EA

AF:

0.000127

AC:

ExAC

AF:

0.000208

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 23, 2021

- -

Hepatitis C virus, susceptibility to

Other:1

not provided, no classification provided

literature only

STRNAD Lab, University Hospital of Ulm

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.2

DANN

Benign

0.69

DEOGEN2

Benign

0.25

T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.017

.;.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.023

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.40

N;N;N;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.87

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.25

MVP

0.71

MPC

0.50

ClinPred

0.018

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.39

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