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NM_033409.4(SLC52A3):c.374C>T (p.Thr125Ile) AND Brown-Vialetto-van Laere syndrome 1

Germline classification:
Likely pathogenic (1 submission)
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:
RCV003334445.1

Allele description [Variation Report for NM_033409.4(SLC52A3):c.374C>T (p.Thr125Ile)]

NM_033409.4(SLC52A3):c.374C>T (p.Thr125Ile)

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.374C>T (p.Thr125Ile)
HGVS:
  • NC_000020.11:g.765401G>A
  • NG_027687.2:g.15585C>T
  • NM_001370085.1:c.374C>T
  • NM_001370086.1:c.374C>T
  • NM_033409.4:c.374C>TMANE SELECT
  • NP_001357014.1:p.Thr125Ile
  • NP_001357015.1:p.Thr125Ile
  • NP_212134.3:p.Thr125Ile
  • LRG_1394t1:c.374C>T
  • LRG_1394:g.15585C>T
  • LRG_1394p1:p.Thr125Ile
  • NC_000020.10:g.746045G>A
Protein change:
T125I
Molecular consequence:
  • NM_001370085.1:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370086.1:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033409.4:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004042655Human Genome Lab, NIMHANS, National Institute of Mental Health and Neuro Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenicgermlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Lab, NIMHANS, National Institute of Mental Health and Neuro Sciences, SCV004042655.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

The missense variant NM_033409.4:c.374C>T (NP_212134.3:p.Thr125Ile) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Thr125Ile variant is novel (not in any individuals) in 1000 Genomes. The p.Thr125Ile variant is novel (not in any individuals) in gnomAD as well as in our inhouse database. There is a moderate physicochemical difference between threonine and isoleucine. The gene SLC52A3 has a low rate of benign missense variation as indicated by a high missense variants Z-Score of 1.25. The gene SLC52A3 contains 12 pathogenic missense variants, indicating that missense variants are a common mechanism of disease in this gene. The p.Thr125Ile missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 125 of SLC52A3 is conserved in all mammalian species. The nucleotide c.374 in SLC52A3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. In addition the clinical phenotype of the proband matches with that caused by pathogenic variants in SLC52A3. For these reasons, this variant has been classified as Uncertain Significance. (PM2 PP2 PP3 PP4_ Moderate PP1)

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

Last Updated: Oct 21, 2023