NM_030777.4(SLC2A10):c.515C>T (p.Thr172Ile) AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 28, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000199609.21

Allele description [Variation Report for NM_030777.4(SLC2A10):c.515C>T (p.Thr172Ile)]

NM_030777.4(SLC2A10):c.515C>T (p.Thr172Ile)

Gene:

SLC2A10:solute carrier family 2 member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_030777.4(SLC2A10):c.515C>T (p.Thr172Ile)

Other names:

p.T172I:ACT>ATT

HGVS:

NC_000020.11:g.46725551C>T
NG_016284.1:g.20912C>T
NM_030777.4:c.515C>TMANE SELECT
NP_110404.1:p.Thr172Ile
NC_000020.10:g.45354190C>T
NM_030777.3:c.515C>T

Protein change:

T172I

Links:

dbSNP: rs143301610

NCBI 1000 Genomes Browser:

rs143301610

Molecular consequence:

NM_030777.4:c.515C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000272444	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (May 14, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001442581	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (May 28, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000272444

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(May 14, 2015)

germline

clinical testing

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

SCV001442581

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(May 28, 2024)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy.

Wooderchak-Donahue W, VanSant-Webb C, Tvrdik T, Plant P, Lewis T, Stocks J, Raney JA, Meyers L, Berg A, Rope AF, Yetman AT, Bleyl SB, Mesley R, Bull DA, Collins RT, Ojeda MM, Roberts A, Lacro R, Woerner A, Stoler J, Bayrak-Toydemir P.

Am J Med Genet A. 2015 Aug;167A(8):1747-57. doi: 10.1002/ajmg.a.37085. Epub 2015 May 5.

PubMed [citation]

PMID:: 25944730

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000272444.3

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

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Thr172Ile in SLC2A10 has not been previously reported in individuals with connective tissue d isorders, but has been identified in 0.1% (8/6610) of Finnish chromosomes and 0. 1% (81/66602) of European chromosomes by the Exome Aggregation Consortium (http: //exac.broadinstitute.org; dbSNP rs143301610). Threonine (Thr) at position 172 i s not conserved in mammals or evolutionarily distant species and several birds, reptiles, and fish carry an isoleucine (Ile) at this position, supporting that t his change may be tolerated. In summary, while the clinical significance of the p.Thr172Ile variant is uncertain, these data suggest that it is more likely to b e benign.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442581.3

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

Description

Variant summary: SLC2A10 c.515C>T (p.Thr172Ile) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 1614086 control chromosomes, predominantly at a frequency of 0.0017 within the Non-Finnish European subpopulation in the gnomAD database (v4.0.0). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is higher than the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016). The variant, c.515C>T, has been reported in the literature in an individual with aortic dilation or dissection, however, further details were not provided on this case (Wooderchak-Donahue_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Arterial Tortuosity Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25944730). ClinVar contains an entry for this variant (Variation ID: 195383). Based on the evidence outlined above, the variant was classified as likely benign.

#	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: Nov 3, 2024

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