rs7212483

Positions:

• chr17-40884800-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000167588.4(KRT20):​c.386G>A​(p.Ser129Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,610,948 control chromosomes in the GnomAD database, including 7,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1502 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6243 hom.)
• Consequence: KRT20 ENST00000167588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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]

LOC105371777 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015886724).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT20	NM_019010.3	c.386G>A	p.Ser129Asn	missense_variant	1/8	ENST00000167588.4	NP_061883.1
LOC105371777	XR_934754.3	n.64-33429C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT20	ENST00000167588.4	c.386G>A	p.Ser129Asn	missense_variant	1/8	1	NM_019010.3	ENSP00000167588	P1
KRT20	ENST00000482529.1	n.111G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18598 AN: 152114 Hom.: 1498 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0929 AC: 23196 AN: 249592 Hom.: 1344 AF XY: 0.0897 AC XY: 12091 AN XY: 134820

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.0132

Gnomad SAS exome AF: 0.0867

Gnomad FIN exome AF: 0.0917

Gnomad NFE exome AF: 0.0832

Gnomad OTH exome AF: 0.0849

GnomAD4 exome AF: 0.0876 AC: 127824 AN: 1458716 Hom.: 6243 Cov.: 32 AF XY: 0.0867 AC XY: 62903 AN XY: 725178

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0702

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.0868

Gnomad4 FIN exome AF: 0.0885

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.122 AC: 18636 AN: 152232 Hom.: 1502 Cov.: 32 AF XY: 0.122 AC XY: 9052 AN XY: 74446

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0798

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0875 Hom.: 1462

Bravo AF: 0.131

TwinsUK AF: 0.0885 AC: 328

ALSPAC AF: 0.0939 AC: 362

ESP6500AA AF: 0.216 AC: 952

ESP6500EA AF: 0.0847 AC: 728

ExAC AF: 0.0948 AC: 11505

Asia WGS AF: 0.0780 AC: 270 AN: 3478

EpiCase AF: 0.0773

EpiControl AF: 0.0772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.36
DANN	Benign	0.15
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.26
ClinPred		0.0025	T
GERP RS		3.3
Varity_R		0.048
gMVP		0.14

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

Other links and lift over

dbSNP: rs7212483; hg19: chr17-39041052; COSMIC: COSV51424418;