NM_033409.4(SLC52A3):c.514A>G (p.Ile172Val) AND Brown-Vialetto-van Laere syndrome 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 2022
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:: RCV001234207.6

Allele description [Variation Report for NM_033409.4(SLC52A3):c.514A>G (p.Ile172Val)]

NM_033409.4(SLC52A3):c.514A>G (p.Ile172Val)

Gene:

SLC52A3:solute carrier family 52 member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p13

Genomic location:

Preferred name:

NM_033409.4(SLC52A3):c.514A>G (p.Ile172Val)

HGVS:

NC_000020.11:g.765261T>C
NG_027687.2:g.15725A>G
NM_001370085.1:c.514A>G
NM_001370086.1:c.514A>G
NM_033409.4:c.514A>GMANE SELECT
NP_001357014.1:p.Ile172Val
NP_001357015.1:p.Ile172Val
NP_212134.3:p.Ile172Val
LRG_1394t1:c.514A>G
LRG_1394:g.15725A>G
LRG_1394p1:p.Ile172Val
NC_000020.10:g.745905T>C
NG_027687.1:g.8324A>G
NM_033409.3:c.514A>G

Protein change:

I172V

Links:

dbSNP: rs201479216

NCBI 1000 Genomes Browser:

rs201479216

Molecular consequence:

NM_001370085.1:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370086.1:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033409.4:c.514A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brown-Vialetto-van Laere syndrome 1
Synonyms:: BULBAR PALSY, PROGRESSIVE, WITH SENSORINEURAL DEAFNESS; PONTOBULBAR PALSY WITH DEAFNESS; Pontobulbar palsy and neurosensory deafness; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024537; MedGen: C0796274; Orphanet: 97229; OMIM: 211530

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001406840	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2022)	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

SCV001406840

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 2022)

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, SCV001406840.4

#	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 isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 172 of the SLC52A3 protein (p.Ile172Val). This variant is present in population databases (rs201479216, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 960645). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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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