NM_001379110.1(SLC9A6):c.15C>G (p.Ile5Met) AND Christianson syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Mar 26, 2021
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV001088949.15

Allele description [Variation Report for NM_001379110.1(SLC9A6):c.15C>G (p.Ile5Met)]

NM_001379110.1(SLC9A6):c.15C>G (p.Ile5Met)

Gene:

SLC9A6:solute carrier family 9 member A6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq26.3

Genomic location:

Preferred name:

NM_001379110.1(SLC9A6):c.15C>G (p.Ile5Met)

HGVS:

NC_000023.11:g.135985673C>G
NG_017160.1:g.5247C>G
NM_001042537.2:c.171C>G
NM_001177651.2:c.15C>G
NM_001330652.2:c.15C>G
NM_001379110.1:c.15C>GMANE SELECT
NM_006359.3:c.171C>G
NP_001036002.1:p.Ile57Met
NP_001036002.1:p.Ile57Met
NP_001171122.1:p.Ile5Met
NP_001317581.1:p.Ile5Met
NP_001366039.1:p.Ile5Met
NP_006350.1:p.Ile57Met
NC_000023.10:g.135067832C>G
NM_001042537.1(SLC9A6):c.171C>G
NM_001042537.1:c.171C>G
NM_006359.2:c.171C>G
p.Ile57Met

Protein change:

I57M

Links:

dbSNP: rs782296172

NCBI 1000 Genomes Browser:

rs782296172

Molecular consequence:

NM_001042537.2:c.171C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001177651.2:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330652.2:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001379110.1:c.15C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006359.3:c.171C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Christianson syndrome (MRXSCH)
Synonyms:: MRXS Christianson; Angelman-like syndrome X-linked; Mental retardation microcephaly epilepsy and ataxia syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010278; MedGen: C2678194; Orphanet: 85278; OMIM: 300243

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000647054	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 24, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001367350	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 29, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001712013	ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	reviewed by expert panel (ClinGen RettAS ACMG Specifications V1)	Likely benign (Mar 26, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000647054

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 24, 2024)

germline

clinical testing

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

SCV001367350

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Aug 29, 2019)

unknown

clinical testing

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

SCV001712013

ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RettAS ACMG Specifications V1)

Likely benign
(Mar 26, 2021)

germline

curation

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, curation
not provided	unknown	yes	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000647054.7

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

#	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 Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001367350.2

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

Description

This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BS2,BP4. This variant was detected in hemizygous state.

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

From ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV001712013.1

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

Description

The allele frequency of the p.Ile5Met variant in SLC9A6 is 0.013% in Ashkenazi Jewish sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). Computational analysis prediction tools suggest that the p.Ile5Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ile5Met variant in SLC9A6 is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4).

#	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: Oct 20, 2024

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