NM_000226.4(KRT9):c.483T>A (p.Asn161Lys) AND Palmoplantar keratoderma, epidermolytic

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 3, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000003136.11

Allele description [Variation Report for NM_000226.4(KRT9):c.483T>A (p.Asn161Lys)]

NM_000226.4(KRT9):c.483T>A (p.Asn161Lys)

Gene:

KRT9:keratin 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_000226.4(KRT9):c.483T>A (p.Asn161Lys)

HGVS:

NC_000017.11:g.41571510A>T
NG_008300.2:g.5549T>A
NM_000226.4:c.483T>AMANE SELECT
NP_000217.2:p.Asn161Lys
NC_000017.10:g.39727762A>T
NG_008300.1:g.5549T>A
NM_000226.3:c.483T>A
P35527:p.Asn161Lys

Protein change:

N161K; ASN161LYS

Links:

UniProtKB: P35527#VAR_003822; OMIM: 607606.0004; dbSNP: rs57536312

NCBI 1000 Genomes Browser:

rs57536312

Molecular consequence:

NM_000226.4:c.483T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Palmoplantar keratoderma, epidermolytic
Synonyms:: Localized epidermolytic hyperkeratosis
Identifiers:: MONDO: MONDO:0968949; MedGen: C1721006; OMIM: PS144200; Human Phenotype Ontology: HP:0007559

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002022618	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 26, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002058972	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] PMID:7523529

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002022618

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 26, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002058972

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 3, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

PMID:7523529

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Revvity Omics, Revvity, SCV002022618.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002058972.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

Same nucleotide change resulting in same amino acid change has been previously reported to be associated with KRT9 related disorder (ClinVar ID: VCV000003000, PMID:7512862, PS1_P). The variant is located in a well-established functional domain or exonic hotspot, where pathogenic variants have frequently reported (PM1_M). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000003003, PMID:7523529,7511021,12192490,14675368, PM5_M).T In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.646, 3CNET: 0.992, PP3_P). A missense variant is a common mechanism associated with Palmoplantar keratoderma (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). herefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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