NM_006941.4(SOX10):c.479T>C (p.Leu160Pro) AND Waardenburg syndrome type 4C

Germline classification:: 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:: RCV003339524.2

Allele description [Variation Report for NM_006941.4(SOX10):c.479T>C (p.Leu160Pro)]

NM_006941.4(SOX10):c.479T>C (p.Leu160Pro)

Genes:

POLR2F:RNA polymerase II, I and III subunit F [Gene - OMIM - HGNC]
SOX10:SRY-box transcription factor 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_006941.4(SOX10):c.479T>C (p.Leu160Pro)

HGVS:

NC_000022.11:g.37978085A>G
NG_007948.1:g.11448T>C
NM_001301130.2:c.294-8069A>G
NM_001301131.2:c.293+10915A>G
NM_001363825.1:c.*38+5775A>G
NM_006941.4:c.479T>CMANE SELECT
NP_008872.1:p.Leu160Pro
NP_008872.1:p.Leu160Pro
LRG_271t1:c.479T>C
LRG_271:g.11448T>C
LRG_271p1:p.Leu160Pro
NC_000022.10:g.38374092A>G
NM_006941.3:c.479T>C

Protein change:

L160P

Links:

dbSNP: rs1482985217

NCBI 1000 Genomes Browser:

rs1482985217

Molecular consequence:

NM_001301130.2:c.294-8069A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001301131.2:c.293+10915A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001363825.1:c.*38+5775A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_006941.4:c.479T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Decreased function

Condition(s)

Name:: Waardenburg syndrome type 4C (WS4C)
Synonyms:: WAARDENBURG SYNDROME WITH HIRSCHSPRUNG DISEASE, TYPE 4C
Identifiers:: MONDO: MONDO:0013202; MedGen: C2750452; Orphanet: 897; OMIM: 613266

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004047529	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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

SCV004047529

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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

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 Neuberg Centre For Genomic Medicine, NCGM, SCV004047529.1

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

Description

The missense variant c.479T>C (p.Leu160Pro) in SOX10 gene has been reported in heterozygous state in individuals affected with Waardenburg Syndrome (Thongpradit, Supranee et al.). Experimental studies have shown that this missense variant p.Leu160Pro suggests a weak dominant-negative mechanism or potential haploinsufficiency associated with the marked decrease of protein produced (Thongpradit, Supranee et al.). The p.Leu160Pro variant is novel (not in any individuals) in gnomAD exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The amino acid Leu at position 160 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties.The amino acid change p.Leu160Pro in SOX10 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 10, 2024

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