NM_006940.6(SOX5):c.1678A>G (p.Met560Val) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 2, 2021
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:: RCV001265682.5

Allele description [Variation Report for NM_006940.6(SOX5):c.1678A>G (p.Met560Val)]

NM_006940.6(SOX5):c.1678A>G (p.Met560Val)

Gene:

SOX5:SRY-box transcription factor 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p12.1

Genomic location:

Preferred name:

NM_006940.6(SOX5):c.1678A>G (p.Met560Val)

HGVS:

NC_000012.12:g.23543304T>C
NG_029612.2:g.1024143A>G
NM_001261414.3:c.1315A>G
NM_001261415.3:c.1648A>G
NM_001330785.2:c.1573A>G
NM_006940.6:c.1678A>GMANE SELECT
NM_152989.5:c.1639A>G
NM_178010.4:c.520A>G
NP_001248343.1:p.Met439Val
NP_001248344.1:p.Met550Val
NP_001317714.1:p.Met525Val
NP_008871.3:p.Met560Val
NP_694534.1:p.Met547Val
NP_821078.1:p.Met174Val
NC_000012.11:g.23696238T>C
NM_006940.4:c.1678A>G
NM_006940.5:c.1678A>G

Protein change:

M174V

Links:

dbSNP: rs1591908609

NCBI 1000 Genomes Browser:

rs1591908609

Molecular consequence:

NM_001261414.3:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001261415.3:c.1648A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330785.2:c.1573A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006940.6:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_152989.5:c.1639A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_178010.4:c.520A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001443849	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 2, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001443849

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 2, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV001443849.4

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

Description

The c.1678A>G (p.M560V) alteration is located in coding exon 13 of the SOX5 gene. This alteration results from an A to G substitution at nucleotide position 1678, causing the methionine (M) at amino acid position 560 to be replaced by a valine (V). Based on data from the Genome Aggregation Database (gnomAD), the SOX5 c.1678A>G alteration was not observed, with coverage at this position. This alteration was reported de novo in two unrelated patients (includes this patient) with language delay and mild intellectual disability (Zawerton, 2020). Other features included seizures and temper tantrums. The p.M560 amino acid is conserved in available vertebrate species. The p.M560V amino acid is located in the SOX5 high-mobility group (HMG) domain which is important for DNA binding and bending, nuclear trafficking, and protein-protein interactions (Zawerton, 2020). Functional studies showed that HMG missense variants prevented SOX5 from binding DNA and from participating in transcriptional activation. The p.M560V alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: Aug 4, 2024

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