chr17-40878274-G-C

Variant summary

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

The NM_019010.3(KRT20):ā€‹c.1010C>Gā€‹(p.Ala337Gly) 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 1,461,864 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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

KRT20
NM_019010.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.385
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19514981).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRT20NM_019010.3 linkuse as main transcriptc.1010C>G p.Ala337Gly missense_variant 6/8 ENST00000167588.4 NP_061883.1 P35900
LOC105371777XR_934754.3 linkuse as main transcriptn.63+27414G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRT20ENST00000167588.4 linkuse as main transcriptc.1010C>G p.Ala337Gly missense_variant 6/81 NM_019010.3 ENSP00000167588.3 P35900

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251444
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsDec 20, 2023The c.1010C>G (p.A337G) alteration is located in exon 6 (coding exon 6) of the KRT20 gene. This alteration results from a C to G substitution at nucleotide position 1010, causing the alanine (A) at amino acid position 337 to be replaced by a glycine (G). 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
0.084
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
0.53
DANN
Benign
0.88
DEOGEN2
Uncertain
0.59
D
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.10
Sift
Benign
0.16
T
Sift4G
Benign
0.17
T
Polyphen
0.012
B
Vest4
0.12
MutPred
0.44
Loss of MoRF binding (P = 0.2123);
MVP
0.61
MPC
0.29
ClinPred
0.10
T
GERP RS
-2.2
Varity_R
0.11
gMVP
0.13

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: rs1347619715; hg19: chr17-39034526; API