NM_018713.3(SLC30A10):c.482G>T (p.Gly161Val) AND Hypermanganesemia with dystonia, polycythemia, and cirrhosis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001101997.5

Allele description [Variation Report for NM_018713.3(SLC30A10):c.482G>T (p.Gly161Val)]

NM_018713.3(SLC30A10):c.482G>T (p.Gly161Val)

Gene:

SLC30A10:solute carrier family 30 member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_018713.3(SLC30A10):c.482G>T (p.Gly161Val)

HGVS:

NC_000001.11:g.219927959C>A
NG_032153.2:g.5693G>T
NM_001376929.1:c.452-854G>T
NM_018713.3:c.482G>TMANE SELECT
NP_061183.2:p.Gly161Val
NC_000001.10:g.220101301C>A
NG_032153.1:g.5693G>T
NM_018713.2:c.482G>T
NR_046437.2:n.599G>T

Protein change:

G161V

Links:

dbSNP: rs1441035788

NCBI 1000 Genomes Browser:

rs1441035788

Molecular consequence:

NM_001376929.1:c.452-854G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_018713.3:c.482G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046437.2:n.599G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMNDYT1)
Synonyms:: Hypermanganesemia with dystonia 1; Hepatic Cirrhosis, Dystonia, Polycythemia and Hypermanganesemia; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013208; MedGen: C2750442; Orphanet: 309854; OMIM: 613280

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001258645	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV005329526	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 20, 2023)	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

SCV001258645

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV005329526

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 20, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Illumina Laboratory Services, Illumina, SCV001258645.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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

From Neuberg Centre For Genomic Medicine, NCGM, SCV005329526.1

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

Description

The observed missense variant c.482G>T (p.Gly161Val) in SLC30A10 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly161Val variant is absent in gnomAD Exomes database. This variant has been submitted to the ClinVar database as Uncertain Significance. Multiple lines of computational evidence (SIFT - tolerated; Polyphen - benign; MutationTaster - polymorphism) predict no damaging effect on protein structure and function for this variant. The amino acid Gly at position 161 is changed to a Val changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). In the absence of another reportable variant in the SLC30A10 gene, the molecular diagnosis is not confirmed.

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

Last Updated: Oct 8, 2024

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