Variant 12-52897550-C-T 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.1330G>A(p.Gly444Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,445,006 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KRT8
NM_002273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.992

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=0.12628767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT8	NM_002273.4 linkuse as main transcript	c.1330G>A	p.Gly444Ser	missense_variant	8/8	ENST00000692008.1	NP_002264.1
KRT8	NM_001256282.2 linkuse as main transcript	c.1414G>A	p.Gly472Ser	missense_variant	9/9		NP_001243211.1
KRT8	NM_001256293.2 linkuse as main transcript	c.1330G>A	p.Gly444Ser	missense_variant	9/9		NP_001243222.1
KRT8	NR_045962.2 linkuse as main transcript	n.1781G>A		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.1330G>A	p.Gly444Ser	missense_variant	8/8		NM_002273.4	ENSP00000509398	P2	P05787-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1445006

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719316

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:

0.0000333

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.1330G>A (p.G444S) alteration is located in exon 8 (coding exon 8) of the KRT8 gene. This alteration results from a G to A substitution at nucleotide position 1330, causing the glycine (G) at amino acid position 444 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

2.8

DANN

Benign

0.95

DEOGEN2

Benign

0.34

T;T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.087

.;.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.26

MutPred

0.14

Gain of phosphorylation at G444 (P = 0.0075);Gain of phosphorylation at G444 (P = 0.0075);Gain of phosphorylation at G444 (P = 0.0075);.;

MVP

0.74

MPC

1.4

ClinPred

0.60

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.079

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over