Variant 12-52180572-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000394815.3(KRT80):c.607G>C(p.Glu203Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,340,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

KRT80
ENST00000394815.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

KRT80 (HGNC:27056): (keratin 80) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene's expression profile shows that it encodes a type II epithelial keratin, although structurally the encoded protein is more like a type II hair keratin. This protein is involved in cell differentiation, localizing near desmosomal plaques in earlier stages of differentiation but then dispersing throughout the cytoplasm in terminally differentiating cells. The type II keratins are clustered in a region of chromosome 12q13. Two transcript variants encoding two different fully functional isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

KRT80 links:

LINC00592 (HGNC:27474): (long intergenic non-protein coding RNA 592)

LINC00592 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT80	NM_182507.3 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/9	ENST00000394815.3	NP_872313.2
KRT80	NM_001081492.2 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/9		NP_001074961.1
KRT80	XM_005268676.4 linkuse as main transcript	c.712G>C	p.Glu238Gln	missense_variant	2/7		XP_005268733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT80	ENST00000394815.3 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/9	1	NM_182507.3	ENSP00000378292	P1	Q6KB66-1
KRT80	ENST00000313234.9 linkuse as main transcript	c.607G>C	p.Glu203Gln	missense_variant	4/9	1		ENSP00000369361		Q6KB66-2
LINC00592	ENST00000640420.1 linkuse as main transcript	n.413+15621C>G		intron_variant, non_coding_transcript_variant		5
KRT80	ENST00000466011.1 linkuse as main transcript	n.763G>C		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000238

AC:

AN:

167898

Hom.:

AF XY:

0.0000226

AC XY:

AN XY:

88582

show subpopulations

Gnomad AFR exome

AF:

0.0000668

Gnomad AMR exome

AF:

0.000170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000373

AC:

AN:

1340350

Hom.:

Cov.:

AF XY:

0.00000458

AC XY:

AN XY:

654364

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.000155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000339

AC:

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

Feb 12, 2024

The c.607G>C (p.E203Q) alteration is located in exon 4 (coding exon 4) of the KRT80 gene. This alteration results from a G to C substitution at nucleotide position 607, causing the glutamic acid (E) at amino acid position 203 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.4

N;N

REVEL

Pathogenic

0.65

Sift

Benign

0.26

T;T

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;D

Vest4

0.57

MutPred

0.66

Loss of ubiquitination at K207 (P = 0.0863);Loss of ubiquitination at K207 (P = 0.0863);

MVP

0.75

MPC

0.54

ClinPred

0.24

GERP RS

4.3

Varity_R

0.29

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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