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NM_003722.5(TP63):c.728G>A (p.Arg243Gln) AND Split hand-foot malformation 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 22, 2022
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:
RCV002250454.1

Allele description [Variation Report for NM_003722.5(TP63):c.728G>A (p.Arg243Gln)]

NM_003722.5(TP63):c.728G>A (p.Arg243Gln)

Gene:
TP63:tumor protein p63 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q28
Genomic location:
Preferred name:
NM_003722.5(TP63):c.728G>A (p.Arg243Gln)
Other names:
R204Q
HGVS:
  • NC_000003.12:g.189864380G>A
  • NG_007550.3:g.272635G>A
  • NM_001114978.2:c.728G>A
  • NM_001114979.2:c.728G>A
  • NM_001114980.2:c.446G>A
  • NM_001114981.2:c.446G>A
  • NM_001114982.2:c.446G>A
  • NM_001329144.2:c.728G>A
  • NM_001329145.2:c.446G>A
  • NM_001329146.2:c.191G>A
  • NM_001329148.2:c.728G>A
  • NM_001329149.2:c.446G>A
  • NM_001329150.2:c.191G>A
  • NM_001329964.2:c.722G>A
  • NM_003722.5:c.728G>AMANE SELECT
  • NP_001108450.1:p.Arg243Gln
  • NP_001108451.1:p.Arg243Gln
  • NP_001108452.1:p.Arg149Gln
  • NP_001108453.1:p.Arg149Gln
  • NP_001108454.1:p.Arg149Gln
  • NP_001316073.1:p.Arg243Gln
  • NP_001316074.1:p.Arg149Gln
  • NP_001316075.1:p.Arg64Gln
  • NP_001316077.1:p.Arg243Gln
  • NP_001316078.1:p.Arg149Gln
  • NP_001316079.1:p.Arg64Gln
  • NP_001316893.1:p.Arg241Gln
  • NP_003713.3:p.Arg243Gln
  • LRG_428t1:c.728G>A
  • LRG_428:g.272635G>A
  • LRG_428p1:p.Arg243Gln
  • NC_000003.11:g.189582169G>A
  • NM_003722.4:c.728G>A
  • Q9H3D4:p.Arg243Gln
Protein change:
R149Q; ARG204GLN
Links:
UniProtKB: Q9H3D4#VAR_020870; OMIM: 603273.0002; dbSNP: rs121908836
NCBI 1000 Genomes Browser:
rs121908836
Molecular consequence:
  • NM_001114978.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114979.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114980.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114981.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114982.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329144.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329145.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329146.2:c.191G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329148.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329149.2:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329150.2:c.191G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329964.2:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003722.5:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Split hand-foot malformation 4
Synonyms:
Split-hand/foot malformation 4; Split-Hand/Foot Malformation Type 4 (SHFM4 syndrome)
Identifiers:
MONDO: MONDO:0011535; MedGen: C1854442; Orphanet: 2440; OMIM: 605289

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0025209983billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 22, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical 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 3billion, SCV002520998.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 0.97). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000006528). A different missense change at the same codon (p.Arg243Trp) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000006527). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024