Variant rs770804000 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182507.3(KRT80):c.1182G>T(p.Met394Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,167,186 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

KRT80
NM_182507.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83

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 rank	MANE	Protein	UniProt
KRT80	NM_182507.3 link	c.1182G>T	p.Met394Ile	missense_variant	Exon 8 of 9	ENST00000394815.3	NP_872313.2	Q6KB66-1
KRT80	NM_001081492.2 link	c.1182G>T	p.Met394Ile	missense_variant	Exon 8 of 9		NP_001074961.1	Q6KB66-2
KRT80	XM_005268676.4 link	c.1287G>T	p.Met429Ile	missense_variant	Exon 6 of 7		XP_005268733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT80	ENST00000394815.3 link	c.1182G>T	p.Met394Ile	missense_variant	Exon 8 of 9	1	NM_182507.3	ENSP00000378292.2	Q6KB66-1
KRT80	ENST00000313234.9 link	c.1182G>T	p.Met394Ile	missense_variant	Exon 8 of 9	1		ENSP00000369361.2	Q6KB66-2
KRT80	ENST00000466011.1 link	n.1338G>T		non_coding_transcript_exon_variant	Exon 6 of 7	2
LINC00592	ENST00000640420.1 link	n.413+6759C>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00000758

AC:

AN:

131918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000660

AC:

AN:

151504

Hom.:

AF XY:

0.0000125

AC XY:

AN XY:

79936

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1035268

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

514026

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000256

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000758

AC:

AN:

131918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63592

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000162

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.43

N;N

REVEL

Uncertain

0.42

Sift

Benign

0.11

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.95

P;P

Vest4

0.44

MutPred

0.36

Gain of catalytic residue at R393 (P = 0.0211);Gain of catalytic residue at R393 (P = 0.0211);

MVP

0.74

MPC

0.34

ClinPred

0.75

GERP RS

4.7

Varity_R

0.31

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over