Genetic Variant NM_182507.3:c.1082G>C (chr12-52172294-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_182507.3(KRT80):c.1082G>C(p.Arg361Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R361Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

KRT80
NM_182507.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0140

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.847

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182507.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT80	NM_182507.3	MANE Select	c.1082G>C	p.Arg361Pro	missense	Exon 7 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.1082G>C	p.Arg361Pro	missense	Exon 7 of 9	NP_001074961.1	Q6KB66-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT80	ENST00000394815.3	TSL:1 MANE Select	c.1082G>C	p.Arg361Pro	missense	Exon 7 of 9	ENSP00000378292.2	Q6KB66-1
KRT80	ENST00000313234.9	TSL:1	c.1082G>C	p.Arg361Pro	missense	Exon 7 of 9	ENSP00000369361.2	Q6KB66-2
KRT80	ENST00000466011.1	TSL:2	n.1238G>C		non_coding_transcript_exon	Exon 5 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Uncertain

0.63

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.70

M_CAP

Benign

0.066

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.4

PhyloP100

-0.014

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

0.89

Vest4

0.67

MutPred

0.67

Loss of MoRF binding (P = 5e-04)

MVP

0.51

MPC

0.47

ClinPred

0.91

GERP RS

-0.79

Varity_R

0.81

gMVP

0.73

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over