NM_005334.3(HCFC1):c.3730C>T (p.Arg1244Cys) AND Methylmalonic acidemia with homocystinuria, type cblX

Clinical significance:Uncertain significance (Last evaluated: Oct 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001291690.1

Allele description [Variation Report for NM_005334.3(HCFC1):c.3730C>T (p.Arg1244Cys)]

NM_005334.3(HCFC1):c.3730C>T (p.Arg1244Cys)

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.3730C>T (p.Arg1244Cys)
HGVS:
  • NC_000023.11:g.153954669G>A
  • NG_012513.1:g.21700C>T
  • NM_005334.3:c.3730C>TMANE SELECT
  • NP_005325.2:p.Arg1244Cys
  • NC_000023.10:g.153220120G>A
  • NM_005334.2:c.3730C>T
Protein change:
R1244C
Links:
dbSNP: rs782155408
NCBI 1000 Genomes Browser:
rs782155408
Molecular consequence:
  • NM_005334.3:c.3730C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001480272New York Genome Center - CSER-NYCKidSeqcriteria provided, single submitter
Uncertain significance
(Oct 5, 2019)
maternalclinical testing

Citation Link

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, SCV001480272.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The hemizyous, maternally inherited c.3730C>T (p.Arg1244Cys) variant identified in the HCFC1 gene substitutes a completely conserved Arginine for Cysteine at amino acid 1244/2036 (coding exon 17/26).This variant is found with low frequency in gnomAD (4 heterozygotes, 0 homozygoes, 0 hemizygotes; allele frequency: 2.412e-5) and ExAC (2 heterozygotes, 0 homozygotes, 0 hemizygotes; allele frequency: 3.165e-5), suggesting it is not a common benign variant in the populations represented in these databases. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. In silico algorithms do not predict this variant is damaging to the function of the canonical transcript, as it is predicted Neutral (Provean; score: -1.79) and Tolerated (SIFT; score: 0.083). The p.Arg1244 reside is within the HCF-proteolysis repeat domain of HCFC1, which is not enriched in pathogenic variants. Given the lack of compelling information regarding its pathogenicity, the c.3730C>T (p.Arg1244Cys) variant identified in the HCFC1 gene is reported here as a Variant of Uncertain Significance.

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

Last Updated: Jan 22, 2022

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