NM_005334.3(HCFC1):c.4687G>A (p.Gly1563Ser) AND Methylmalonic acidemia with homocystinuria, type cblX

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2021
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:: RCV001327000.5

Allele description [Variation Report for NM_005334.3(HCFC1):c.4687G>A (p.Gly1563Ser)]

NM_005334.3(HCFC1):c.4687G>A (p.Gly1563Ser)

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.4687G>A (p.Gly1563Ser)

HGVS:

NC_000023.11:g.153952769C>T
NG_012513.1:g.23600G>A
NM_005334.3:c.4687G>AMANE SELECT
NP_005325.2:p.Gly1563Ser
NC_000023.10:g.153218220C>T

Protein change:

G1563S

Links:

dbSNP: rs782310209

NCBI 1000 Genomes Browser:

rs782310209

Molecular consequence:

NM_005334.3:c.4687G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001518057	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001518057

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001518057.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glycine with serine at codon 1563 of the HCFC1 protein (p.Gly1563Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs782310209, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with HCFC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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