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NM_003545.4(H4C5):c.136C>T (p.Arg46Cys) AND not specified

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 13, 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:
RCV004030242.1

Allele description [Variation Report for NM_003545.4(H4C5):c.136C>T (p.Arg46Cys)]

NM_003545.4(H4C5):c.136C>T (p.Arg46Cys)

Genes:
LOC129996027:ATAC-STARR-seq lymphoblastoid active region 24208 [Gene]
H4C5:H4 clustered histone 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p22.2
Genomic location:
Preferred name:
NM_003545.4(H4C5):c.136C>T (p.Arg46Cys)
Other names:
H4C5, ARG46CYS
HGVS:
  • NC_000006.12:g.26204780C>T
  • NM_003545.4:c.136C>TMANE SELECT
  • NP_003536.1:p.Arg46Cys
  • NC_000006.11:g.26205008C>T
  • NM_003545.3:c.136C>T
Protein change:
R46C; ARG46CYS
Links:
OMIM: 602830.0004; dbSNP: rs950721550
NCBI 1000 Genomes Browser:
rs950721550
Molecular consequence:
  • NM_003545.4:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004067378Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 13, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome.

Tessadori F, Duran K, Knapp K, Fellner M; Deciphering Developmental Disorders Study., Smithson S, Beleza Meireles A, Elting MW, Waisfisz Q, O'Donnell-Luria A, Nowak C, Douglas J, Ronan A, Brunet T, Kotzaeridou U, Svihovec S, Saenz MS, Thiffault I, Del Viso F, Devine P, Rego S, Tenney J, et al.

Am J Hum Genet. 2022 Apr 7;109(4):750-758. doi: 10.1016/j.ajhg.2022.02.003. Epub 2022 Feb 23.

PubMed [citation]
PMID:
35202563
PMCID:
PMC9069069

Details of each submission

From Ambry Genetics, SCV004067378.2

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

Description

The c.136C>T (p.R46C) alteration is located in exon 1 (coding exon 1) of the HIST1H4E gene. This alteration results from a C to T substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with H4C5-related Tessadori-van Haaften neurodevelopmental syndrome (Tessadori, 2022). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: May 19, 2024