17-40876402-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000167588.4(KRT20):​c.1234G>T​(p.Val412Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

KRT20
ENST00000167588.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.802
Variant links:
Genes affected
KRT20 (HGNC:20412): (keratin 20) The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This cytokeratin is a major cellular protein of mature enterocytes and goblet cells and is specifically expressed in the gastric and intestinal mucosa. The type I cytokeratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41054222).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRT20NM_019010.3 linkuse as main transcriptc.1234G>T p.Val412Phe missense_variant 8/8 ENST00000167588.4 NP_061883.1 P35900
LOC105371777XR_934754.3 linkuse as main transcriptn.63+25542C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRT20ENST00000167588.4 linkuse as main transcriptc.1234G>T p.Val412Phe missense_variant 8/81 NM_019010.3 ENSP00000167588.3 P35900

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152174
Hom.:
0
Cov.:
32
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000915
AC:
23
AN:
251354
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000609
AC:
89
AN:
1461090
Hom.:
0
Cov.:
29
AF XY:
0.0000619
AC XY:
45
AN XY:
726888
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000603
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74334
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 26, 2024The c.1234G>T (p.V412F) alteration is located in exon 8 (coding exon 8) of the KRT20 gene. This alteration results from a G to T substitution at nucleotide position 1234, causing the valine (V) at amino acid position 412 to be replaced by a phenylalanine (F). 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Uncertain
0.10
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.56
D
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.41
T
MetaSVM
Uncertain
0.68
D
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.98
D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.6
D
REVEL
Pathogenic
0.74
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.89
P
Vest4
0.46
MVP
0.94
MPC
0.37
ClinPred
0.37
T
GERP RS
3.1
Varity_R
0.53
gMVP
0.80

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: rs758535549; hg19: chr17-39032654; API