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NM_005334.3(HCFC1):c.3257G>A (p.Gly1086Asp) AND Methylmalonic acidemia with homocystinuria, type cblX

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 28, 2019
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:
RCV001291632.1

Allele description [Variation Report for NM_005334.3(HCFC1):c.3257G>A (p.Gly1086Asp)]

NM_005334.3(HCFC1):c.3257G>A (p.Gly1086Asp)

Gene:
HCFC1:host cell factor C1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_005334.3(HCFC1):c.3257G>A (p.Gly1086Asp)
HGVS:
  • NC_000023.11:g.153955142C>T
  • NG_012513.1:g.21227G>A
  • NM_005334.3:c.3257G>AMANE SELECT
  • NP_005325.2:p.Gly1086Asp
  • NC_000023.10:g.153220593C>T
  • NM_005334.2:c.3257G>A
Protein change:
G1086D
Links:
dbSNP: rs2065362050
NCBI 1000 Genomes Browser:
rs2065362050
Molecular consequence:
  • NM_005334.3:c.3257G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Methylmalonic acidemia with homocystinuria, type cblX (MAHCX)
Synonyms:
INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 3
Identifiers:
MONDO: MONDO:0010657; MedGen: C0796208; Orphanet: 369962; OMIM: 309541

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001480206New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Uncertain significance
(Aug 28, 2019) 		maternalclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedmaternalunknown1not providednot provided1not providedclinical testing

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV001480206.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The hemizygous c.3257G>A (p.Gly1086Asp) variant identified in the HCFC1 gene substitutes a completely conserved Glycine for Aspartic Acid at amino acid 1086/2036 (coding exon 17/26). This variant is absent from gnomAD and ExAC suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant to be Deleterious (Provean; score: -3.08) and Damaging (SIFT; score: 0.00) to the function of the canonical transcript.This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The Gly1086 residue is within the basic HCF-1 Pro domain of HCFC1, and missense variants within this domain and throughout the protein have been reported in affected individuals [PMID: 25740848]. Given the lack of compelling information regarding the pathogenicity of the c.3257G>A (p.Gly1086Asp) variant it is reported here as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalunknown1not providednot provided1not providednot providednot provided

Last Updated: Sep 1, 2024