NM_138773.4(SLC25A46):c.209C>G (p.Ser70Cys) AND Neuropathy, hereditary motor and sensory, type 6B

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 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:: RCV001225986.8

Allele description [Variation Report for NM_138773.4(SLC25A46):c.209C>G (p.Ser70Cys)]

NM_138773.4(SLC25A46):c.209C>G (p.Ser70Cys)

Gene:

SLC25A46:solute carrier family 25 member 46 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.1

Genomic location:

Preferred name:

NM_138773.4(SLC25A46):c.209C>G (p.Ser70Cys)

HGVS:

NC_000005.10:g.110739328C>G
NG_051334.1:g.6193C>G
NM_001303249.3:c.209C>G
NM_001303250.3:c.10+1081C>G
NM_138773.4:c.209C>GMANE SELECT
NP_001290178.1:p.Ser70Cys
NP_620128.1:p.Ser70Cys
LRG_1091t1:c.209C>G
LRG_1091:g.6193C>G
LRG_1091p1:p.Ser70Cys
NC_000005.9:g.110075029C>G
NM_138773.2:c.209C>G
NR_138151.2:n.322C>G

Protein change:

S70C

Links:

dbSNP: rs904962071

NCBI 1000 Genomes Browser:

rs904962071

Molecular consequence:

NM_001303250.3:c.10+1081C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001303249.3:c.209C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_138773.4:c.209C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_138151.2:n.322C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Neuropathy, hereditary motor and sensory, type 6B (HMSN6B)
Synonyms:: HMSN VIB; CHARCOT-MARIE-TOOTH DISEASE, TYPE 6B; NEUROPATHY, HEREDITARY MOTOR AND SENSORY, TYPE VIB, WITH OPTIC ATROPHY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0014671; MedGen: C4225302; OMIM: 616505

Recent activity

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RecName: Full=Ubiquitin carboxyl-terminal hydrolase 45; AltName: Full=Deubiquiti...
RecName: Full=Ubiquitin carboxyl-terminal hydrolase 45; AltName: Full=Deubiquitinating enzyme 45; AltName: Full=Ubiquitin thioesterase 45; AltName: Full=Ubiquitin-specific-processing protease 45
gi|296453002|sp|Q70EL2.3|UBP45_HUMA

Protein
ras-related protein Ral-B [Mus musculus]
ras-related protein Ral-B [Mus musculus]
gi|11612509|ref|NP_071722.1|

Protein
Homo sapiens mRNA adjacent to 3' end of integrated HPV16 (INT259)
Homo sapiens mRNA adjacent to 3' end of integrated HPV16 (INT259)
gi|18873710|emb|AJ431609.1|

Nucleotide
Leber congenital amaurosis 19
Leber congenital amaurosis 19

MedGen
C5193139[conceptid] (1)
MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001398280	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2019)	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

SCV001398280

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2019)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001398280.5

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

Description

This variant has not been reported in the literature in individuals with SLC25A46-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 70 of the SLC25A46 protein (p.Ser70Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine.

#	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: Sep 29, 2024

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