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NM_000424.4(KRT5):c.527A>G (p.Asn176Ser) AND Epidermolysis bullosa simplex with mottled pigmentation

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 23, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003152677.1

Allele description [Variation Report for NM_000424.4(KRT5):c.527A>G (p.Asn176Ser)]

NM_000424.4(KRT5):c.527A>G (p.Asn176Ser)

Gene:
KRT5:keratin 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000424.4(KRT5):c.527A>G (p.Asn176Ser)
HGVS:
  • NC_000012.12:g.52519770T>C
  • NG_008297.1:g.5690A>G
  • NM_000424.4:c.527A>GMANE SELECT
  • NP_000415.2:p.Asn176Ser
  • NC_000012.11:g.52913554T>C
  • NM_000424.3:c.527A>G
  • P13647:p.Asn176Ser
Protein change:
N176S
Links:
UniProtKB: P13647#VAR_010457; dbSNP: rs59092197
NCBI 1000 Genomes Browser:
rs59092197
Molecular consequence:
  • NM_000424.4:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Epidermolysis bullosa simplex with mottled pigmentation (EBS2F)
Synonyms:
SPECKLED HYPERPIGMENTATION WITH PUNCTATE PALMOPLANTAR KERATOSES AND CHILDHOOD BLISTERING; EBS with mottled pigmentation; Speckled hyperpigmentation, palmo-plantar punctate keratoses and childhood blistering; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007556; MedGen: C0432316; Orphanet: 79397; OMIM: 131960

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0038415233billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Feb 23, 2023) 		unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Primers for exon-specific amplification of the KRT5 gene: identification of novel and recurrent mutations in epidermolysis bullosa simplex patients.

Stephens K, Ehrlich P, Weaver M, Le R, Spencer A, Sybert VP.

J Invest Dermatol. 1997 Mar;108(3):349-53.

PubMed [citation]
PMID:
9036937

An overview of the genetic basis of epidermolysis bullosa in Brazil: discovery of novel and recurrent disease-causing variants.

Mariath LM, Santin JT, Frantz JA, Doriqui MJR, Kiszewski AE, Schuler-Faccini L.

Clin Genet. 2019 Sep;96(3):189-198. doi: 10.1111/cge.13555. Epub 2019 May 29. Review.

PubMed [citation]
PMID:
31001817
See all PubMed Citations (3)

Details of each submission

From 3billion, SCV003841523.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with KRT5-related disorder (PMID: 9036937). However, the evidence of pathogenicity is insufficient at this time. A different missense change at the same codon (p.Asn176Lys) has been reported to be associated with KRT5 related disorder (PMID: 31001817). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2023