NM_005413.4(SIX3):c.109G>T (p.Gly37Cys) AND not provided

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Apr 1, 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:: RCV000713302.20

Allele description [Variation Report for NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)]

NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)

Gene:

SIX3:SIX homeobox 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)

HGVS:

NC_000002.12:g.44942213G>T
NG_016222.1:g.5316G>T
NM_005413.4:c.109G>TMANE SELECT
NP_005404.1:p.Gly37Cys
NC_000002.11:g.45169352G>T
NM_005413.3:c.109G>T
O95343:p.Gly37Cys

Protein change:

G37C; GLY37CYS

Links:

UniProtKB: O95343#VAR_071335; OMIM: 603714.0009; dbSNP: rs199823175

NCBI 1000 Genomes Browser:

rs199823175

Molecular consequence:

NM_005413.4:c.109G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490797	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Feb 11, 2019)	germline	clinical testing	Citation Link,
SCV000843892	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Jul 12, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18791198, 20157829, 19346217, 26080100, 26467025
SCV004011150	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Apr 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490797

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Feb 11, 2019)

germline

clinical testing

Citation Link,

SCV000843892

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Benign
(Jul 12, 2018)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004011150

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Benign
(Apr 1, 2023)

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
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the human SIX3 gene in holoprosencephaly are loss of function.

Domené S, Roessler E, El-Jaick KB, Snir M, Brown JL, Vélez JI, Bale S, Lacbawan F, Muenke M, Feldman B.

Hum Mol Genet. 2008 Dec 15;17(24):3919-28. doi: 10.1093/hmg/ddn294. Epub 2008 Sep 12.

PubMed [citation]

PMID:: 18791198
PMCID:: PMC2733808

Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly.

Hehr U, Pineda-Alvarez DE, Uyanik G, Hu P, Zhou N, Hehr A, Schell-Apacik C, Altus C, Daumer-Haas C, Meiner A, Steuernagel P, Roessler E, Winkler J, Muenke M.

Hum Genet. 2010 Mar;127(5):555-61. doi: 10.1007/s00439-010-0797-4. Epub 2010 Feb 16.

PubMed [citation]

PMID:: 20157829
PMCID:: PMC4101187

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000490797.4

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

Description

This variant is associated with the following publications: (PMID: 18791198, 26080100, 20157829, 19346217)

#	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

From Athena Diagnostics, SCV000843892.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV004011150.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

SIX3: BS1, BS2

#	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		2	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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