12-52172201-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182507.3(KRT80):​c.1175G>A​(p.Gly392Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

KRT80
NM_182507.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.563
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)

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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=0.095629305).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT80NM_182507.3 linkc.1175G>A p.Gly392Asp missense_variant Exon 7 of 9 ENST00000394815.3 NP_872313.2 Q6KB66-1
KRT80NM_001081492.2 linkc.1175G>A p.Gly392Asp missense_variant Exon 7 of 9 NP_001074961.1 Q6KB66-2
KRT80XM_005268676.4 linkc.1280G>A p.Gly427Asp missense_variant Exon 5 of 7 XP_005268733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT80ENST00000394815.3 linkc.1175G>A p.Gly392Asp missense_variant Exon 7 of 9 1 NM_182507.3 ENSP00000378292.2 Q6KB66-1
KRT80ENST00000313234.9 linkc.1175G>A p.Gly392Asp missense_variant Exon 7 of 9 1 ENSP00000369361.2 Q6KB66-2
KRT80ENST00000466011.1 linkn.1331G>A non_coding_transcript_exon_variant Exon 5 of 7 2
LINC00592ENST00000640420.1 linkn.413+7250C>T intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461026
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726856
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1175G>A (p.G392D) alteration is located in exon 7 (coding exon 7) of the KRT80 gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the glycine (G) at amino acid position 392 to be replaced by an aspartic acid (D). 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
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.094
.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.37
T;T
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.096
T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
-0.14
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.090
N;N
REVEL
Benign
0.13
Sift
Benign
0.23
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.0010
B;B
Vest4
0.12
MVP
0.45
MPC
0.17
ClinPred
0.38
T
GERP RS
3.7
Varity_R
0.10
gMVP
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371482488; hg19: chr12-52565985; API