NM_006941.4(SOX10):c.294C>G (p.Ser98Arg) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 13, 2024
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:: RCV003055612.11

Allele description [Variation Report for NM_006941.4(SOX10):c.294C>G (p.Ser98Arg)]

NM_006941.4(SOX10):c.294C>G (p.Ser98Arg)

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.294C>G (p.Ser98Arg)

HGVS:

NC_000022.11:g.37983491G>C
NG_007948.1:g.6042C>G
NG_148296.1:g.768G>C
NM_001301130.2:c.294-2663G>C
NM_001301131.2:c.293+16321G>C
NM_001363825.1:c.*38+11181G>C
NM_006941.4:c.294C>GMANE SELECT
NP_008872.1:p.Ser98Arg
NP_008872.1:p.Ser98Arg
LRG_271t1:c.294C>G
LRG_271:g.6042C>G
LRG_271p1:p.Ser98Arg
NC_000022.10:g.38379498G>C
NM_006941.3:c.294C>G

Protein change:

S98R

Molecular consequence:

NM_001301130.2:c.294-2663G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001301131.2:c.293+16321G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001363825.1:c.*38+11181G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_006941.4:c.294C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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ubiquitin domain-containing protein UBFD1 isoform X4 [Homo sapiens]
ubiquitin domain-containing protein UBFD1 isoform X4 [Homo sapiens]
gi|2217306718|ref|XP_047290323.1|

Protein
ubiquitin domain-containing protein UBFD1 isoform X3 [Homo sapiens]
ubiquitin domain-containing protein UBFD1 isoform X3 [Homo sapiens]
gi|2462549892|ref|XP_054169471.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003348240	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005389433	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 13, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003348240

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 22, 2022)

germline

clinical testing

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

SCV005389433

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 13, 2024)

germline

clinical testing

Citation Link

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

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, SCV003348240.2

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

Description

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. This variant has not been reported in the literature in individuals affected with SOX10-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 98 of the SOX10 protein (p.Ser98Arg).

#	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 GeneDx, SCV005389433.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	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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