NM_001114748.2(TMEM240):c.239C>T (p.Thr80Met) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 1, 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:: RCV003546479.9

Allele description [Variation Report for NM_001114748.2(TMEM240):c.239C>T (p.Thr80Met)]

NM_001114748.2(TMEM240):c.239C>T (p.Thr80Met)

Gene:

TMEM240:transmembrane protein 240 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_001114748.2(TMEM240):c.239C>T (p.Thr80Met)

HGVS:

NC_000001.11:g.1535723G>A
NG_041807.1:g.9638C>T
NG_053035.1:g.28581G>A
NM_001114748.2:c.239C>TMANE SELECT
NP_001108220.1:p.Thr80Met
NC_000001.10:g.1471103G>A
NM_001114748.1:c.239C>T
Q5SV17:p.Thr80Met

Protein change:

T80M; THR80MET

Links:

UniProtKB: Q5SV17#VAR_071906; OMIM: 616101.0004; dbSNP: rs606231454

NCBI 1000 Genomes Browser:

rs606231454

Molecular consequence:

NM_001114748.2:c.239C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Euonymus microcarpus isolate PW external transcribed spacer and 18S ribosomal RN...
Euonymus microcarpus isolate PW external transcribed spacer and 18S ribosomal RNA gene, partial sequence
gi|572168839|gb|KF282060.1|

Nucleotide
Homo sapiens serum response factor binding protein 1 (SRFBP1), mRNA
Homo sapiens serum response factor binding protein 1 (SRFBP1), mRNA
gi|1653961462|ref|NM_152546.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004269456	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25070513, 28492532
SCV004700942	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Feb 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004269456

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 11, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004700942

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Uncertain significance
(Feb 1, 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	1	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

TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment.

Delplanque J, Devos D, Huin V, Genet A, Sand O, Moreau C, Goizet C, Charles P, Anheim M, Monin ML, Buée L, Destée A, Grolez G, Delmaire C, Dujardin K, Dellacherie D, Brice A, Stevanin G, Strubi-Vuillaume I, Dürr A, Sablonnière B.

Brain. 2014 Oct;137(Pt 10):2657-63. doi: 10.1093/brain/awu202. Epub 2014 Jul 28.

PubMed [citation]

PMID:: 25070513

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, SCV004269456.1

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

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 161195). This missense change has been observed in individual(s) with spinocerebellar ataxia (PMID: 25070513). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs606231454, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 80 of the TMEM240 protein (p.Thr80Met).

#	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, SCV004700942.7

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

Description

TMEM240: PM2, PS4:Moderate, PS3:Supporting

#	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		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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