Variant 12-52904822-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5

The NM_002273.4(KRT8):c.160T>A(p.Tyr54Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y54C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRT8
NM_002273.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

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:

KRT8 (HGNC:):

KRT8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT8	NM_002273.4 linkuse as main transcript	c.160T>A	p.Tyr54Asn	missense_variant	1/8	ENST00000692008.1	NP_002264.1	P05787-1
KRT8	NM_001256282.2 linkuse as main transcript	c.244T>A	p.Tyr82Asn	missense_variant	2/9		NP_001243211.1	Q7L4M3
KRT8	NM_001256293.2 linkuse as main transcript	c.160T>A	p.Tyr54Asn	missense_variant	2/9		NP_001243222.1	P05787-1
KRT8	NR_045962.2 linkuse as main transcript	n.611T>A		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000692008.1 linkuse as main transcript	c.160T>A	p.Tyr54Asn	missense_variant	1/8		NM_002273.4	ENSP00000509398.1		P05787-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248332

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460166

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726402

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

0.00086

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Uncertain

0.68

D;D;D;.;.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.19

.;.;T;T;T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.6

H;H;H;.;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.025

D;D;D;D;D;D;D

Sift4G

Uncertain

0.024

D;D;D;D;.;.;D

Polyphen

0.59

P;P;P;.;.;.;.

Vest4

0.45

MutPred

0.56

Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);.;Gain of disorder (P = 0.0498);.;.;

MVP

0.91

MPC

1.6

ClinPred

0.40

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.51

gMVP

0.67

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over