17-40819076-G-C

Variant summary

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

The NM_000421.5(KRT10):ā€‹c.1459C>Gā€‹(p.His487Asp) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 24)
Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.352
Variant links:
Genes affected
KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]
KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.07825872).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT10NM_000421.5 linkc.1459C>G p.His487Asp missense_variant Exon 7 of 8 ENST00000269576.6 NP_000412.4 P13645
KRT10NM_001379366.1 linkc.1459C>G p.His487Asp missense_variant Exon 7 of 8 NP_001366295.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT10ENST00000269576.6 linkc.1459C>G p.His487Asp missense_variant Exon 7 of 8 1 NM_000421.5 ENSP00000269576.5 P13645

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
138232
Hom.:
0
Cov.:
24
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
109
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
138232
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
67180
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
4.2
DANN
Benign
0.79
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.61
N
REVEL
Benign
0.24
Sift
Benign
0.079
T
Sift4G
Benign
0.20
T
Polyphen
0.0010
B
Vest4
0.32
MutPred
0.28
Gain of relative solvent accessibility (P = 0.0483);
MVP
0.52
MPC
0.58
ClinPred
0.067
T
GERP RS
-1.5
Varity_R
0.18
gMVP
0.52

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: rs17855579; hg19: chr17-38975328; API