12-52949280-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000224.3(KRT18):āc.107A>Gā(p.Tyr36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,444 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: not found (cov: 40)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
KRT18
NM_000224.3 missense
NM_000224.3 missense
Scores
5
8
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.06
Genes affected
KRT18 (HGNC:6430): (keratin 18) KRT18 encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a modified_residue Phosphotyrosine (size 0) in uniprot entity K1C18_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT18 | NM_000224.3 | c.107A>G | p.Tyr36Cys | missense_variant | Exon 1 of 7 | ENST00000388835.4 | NP_000215.1 | |
KRT18 | NM_199187.2 | c.107A>G | p.Tyr36Cys | missense_variant | Exon 2 of 8 | NP_954657.1 | ||
KRT8 | NM_001256293.2 | c.-47+435T>C | intron_variant | Intron 1 of 8 | NP_001243222.1 | |||
KRT8 | NR_045962.2 | n.405+176T>C | intron_variant | Intron 1 of 8 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 40
GnomAD3 genomes
Cov.:
40
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458444Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 725544
GnomAD4 exome
AF:
AC:
2
AN:
1458444
Hom.:
Cov.:
36
AF XY:
AC XY:
1
AN XY:
725544
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 40
GnomAD4 genome
Cov.:
40
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;.
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of catalytic residue at G40 (P = 0);Gain of catalytic residue at G40 (P = 0);Gain of catalytic residue at G40 (P = 0);
MVP
MPC
0.73
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at