rs148980872

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_182507.3(KRT80):​c.811G>C​(p.Glu271Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E271K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

KRT80
NM_182507.3 missense

Scores

2
13
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29
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]
LINC00592 (HGNC:27474): (long intergenic non-protein coding RNA 592)

Genome browser will be placed here

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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT80NM_182507.3 linkc.811G>C p.Glu271Gln missense_variant Exon 5 of 9 ENST00000394815.3 NP_872313.2 Q6KB66-1
KRT80NM_001081492.2 linkc.811G>C p.Glu271Gln missense_variant Exon 5 of 9 NP_001074961.1 Q6KB66-2
KRT80XM_005268676.4 linkc.916G>C p.Glu306Gln missense_variant Exon 3 of 7 XP_005268733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT80ENST00000394815.3 linkc.811G>C p.Glu271Gln missense_variant Exon 5 of 9 1 NM_182507.3 ENSP00000378292.2 Q6KB66-1
KRT80ENST00000313234.9 linkc.811G>C p.Glu271Gln missense_variant Exon 5 of 9 1 ENSP00000369361.2 Q6KB66-2
KRT80ENST00000466011.1 linkn.967G>C non_coding_transcript_exon_variant Exon 3 of 7 2
LINC00592ENST00000640420.1 linkn.413+8669C>G intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152144
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249580
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135098
show subpopulations
Gnomad AFR exome
AF:
0.0000617
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1460480
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726646
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152144
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74332
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
.;D
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.058
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.044
D;D
Polyphen
0.99
D;D
Vest4
0.70
MutPred
0.76
Gain of catalytic residue at Y273 (P = 0.0621);Gain of catalytic residue at Y273 (P = 0.0621);
MVP
0.70
MPC
0.49
ClinPred
0.92
D
GERP RS
2.4
Varity_R
0.35
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs148980872; hg19: chr12-52567404; API