rs7212483

Variant names:

• chr17-40884800-C-T
• rs7212483
• NM_019010.3:c.386G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019010.3(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. 16/21 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: 𝑓 0.12 (1502 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6243 hom.)
• Consequence: KRT20 NM_019010.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 20 publications found

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]

KRT20 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000265359 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KRT20	NM_019010.3	c.386G>A	p.Ser129Asn	missense_variant	Exon 1 of 8	ENST00000167588.4	NP_061883.1
LOC105371777	XR_934754.3	n.64-33429C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT20	ENST00000167588.4	c.386G>A	p.Ser129Asn	missense_variant	Exon 1 of 8	1	NM_019010.3	ENSP00000167588.3
KRT20	ENST00000482529.1	n.111G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000265359	ENST00000818906.1	n.175+6969C>T		intron_variant	Intron 2 of 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

GnomAD2 exomes AF: 0.0929 AC: 23196 AN: 249592 AF XY: 0.0897

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 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

African (AFR) AF: 0.232 AC: 7756 AN: 33406

American (AMR) AF: 0.117 AC: 5232 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1822 AN: 25966

East Asian (EAS) AF: 0.0131 AC: 518 AN: 39632

South Asian (SAS) AF: 0.0868 AC: 7460 AN: 85916

European-Finnish (FIN) AF: 0.0885 AC: 4722 AN: 53350

Middle Eastern (MID) AF: 0.0959 AC: 552 AN: 5756

European-Non Finnish (NFE) AF: 0.0850 AC: 94346 AN: 1109834

Other (OTH) AF: 0.0899 AC: 5416 AN: 60260

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

African (AFR) AF: 0.224 AC: 9289 AN: 41498

American (AMR) AF: 0.121 AC: 1848 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5188

South Asian (SAS) AF: 0.0798 AC: 385 AN: 4822

European-Finnish (FIN) AF: 0.0882 AC: 936 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0818 AC: 5564 AN: 68024

Other (OTH) AF: 0.103 AC: 218 AN: 2116

Alfa AF: 0.0954 Hom.: 2608

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
PhyloP100		-0.23
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
PromoterAI		0.061	Neutral
Varity_R		0.048
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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