Variant 12-52897520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002273.4(KRT8):c.1360C>T(p.Arg454Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000626 in 1,598,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KRT8
NM_002273.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12309995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT8	NM_002273.4 linkuse as main transcript	c.1360C>T	p.Arg454Cys	missense_variant	8/8	ENST00000692008.1	NP_002264.1
KRT8	NM_001256282.2 linkuse as main transcript	c.1444C>T	p.Arg482Cys	missense_variant	9/9		NP_001243211.1
KRT8	NM_001256293.2 linkuse as main transcript	c.1360C>T	p.Arg454Cys	missense_variant	9/9		NP_001243222.1
KRT8	NR_045962.2 linkuse as main transcript	n.1811C>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.1360C>T	p.Arg454Cys	missense_variant	8/8		NM_002273.4	ENSP00000509398	P2	P05787-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000847

AC:

AN:

236064

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

128952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000484

AC:

AN:

1446382

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719968

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000830

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.33

T;T;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.079

.;.;T;T

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.3

L;L;L;.

MutationTaster

Benign

0.95

D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.33

MutPred

0.30

Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);.;

MVP

0.81

MPC

0.69

ClinPred

0.27

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.38

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