NM_015087.5(SPART):c.68C>A (p.Ala23Asp) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Oct 15, 2021
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:: RCV000483605.16

Allele description [Variation Report for NM_015087.5(SPART):c.68C>A (p.Ala23Asp)]

NM_015087.5(SPART):c.68C>A (p.Ala23Asp)

Gene:

SPART:spartin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.3

Genomic location:

Preferred name:

NM_015087.5(SPART):c.68C>A (p.Ala23Asp)

HGVS:

NC_000013.11:g.36335763G>T
NG_011559.2:g.39418C>A
NM_001142294.2:c.68C>A
NM_001142295.2:c.68C>A
NM_001142296.2:c.68C>A
NM_015087.5:c.68C>AMANE SELECT
NP_001135766.1:p.Ala23Asp
NP_001135767.1:p.Ala23Asp
NP_001135768.1:p.Ala23Asp
NP_055902.1:p.Ala23Asp
NC_000013.10:g.36909900G>T
NM_015087.4:c.68C>A
p.Ala23Asp

Protein change:

A23D

Links:

dbSNP: rs753340463

NCBI 1000 Genomes Browser:

rs753340463

Molecular consequence:

NM_001142294.2:c.68C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001142295.2:c.68C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001142296.2:c.68C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015087.5:c.68C>A - 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
SCV000574250	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Mar 22, 2017)	germline	clinical testing	Citation Link,
SCV001491256	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001713622	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 15, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000574250

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Mar 22, 2017)

germline

clinical testing

Citation Link,

SCV001491256

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 15, 2021)

germline

clinical testing

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

SCV001713622

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 15, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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 GeneDx, SCV000574250.3

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

Description

A variant of uncertain significance has been identified in the SPG20 gene. The A23D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A23D variant is observed in 22/11548 (0.2%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A23D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants have not been reported in Human Gene Mutation Database in association with SPG20-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001491256.3

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

Description

This sequence change replaces alanine with aspartic acid at codon 23 of the SPART protein (p.Ala23Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs753340463, ExAC 0.2%). This variant has not been reported in the literature in individuals affected with SPART-related conditions. ClinVar contains an entry for this variant (Variation ID: 424442). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001713622.1

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

Last Updated: Nov 24, 2024

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