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NM_003119.4(SPG7):c.1033G>C (p.Ala345Pro) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 15, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003235255.1

Allele description [Variation Report for NM_003119.4(SPG7):c.1033G>C (p.Ala345Pro)]

NM_003119.4(SPG7):c.1033G>C (p.Ala345Pro)

Gene:
SPG7:SPG7 matrix AAA peptidase subunit, paraplegin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_003119.4(SPG7):c.1033G>C (p.Ala345Pro)
HGVS:
  • NC_000016.10:g.89531949G>C
  • NG_008082.1:g.28553G>C
  • NM_001363850.1:c.1033G>C
  • NM_003119.4:c.1033G>CMANE SELECT
  • NM_199367.3:c.1033G>C
  • NP_001350779.1:p.Ala345Pro
  • NP_003110.1:p.Ala345Pro
  • NP_955399.1:p.Ala345Pro
  • NC_000016.9:g.89598357G>C
  • NM_003119.2:c.1033G>C
  • NM_003119.3:c.1033G>C
Protein change:
A345P
Links:
dbSNP: rs368373840
NCBI 1000 Genomes Browser:
rs368373840
Molecular consequence:
  • NM_001363850.1:c.1033G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003119.4:c.1033G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_199367.3:c.1033G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003934860Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(May 15, 2023)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.

Sun M, Johnson AK, Nelakuditi V, Guidugli L, Fischer D, Arndt K, Ma L, Sandford E, Shakkottai V, Boycott K, Warman-Chardon J, Li Z, Del Gaudio D, Burmeister M, Gomez CM, Waggoner DJ, Das S.

Genet Med. 2019 Jan;21(1):195-206. doi: 10.1038/s41436-018-0007-7. Epub 2018 Jun 18.

PubMed [citation]
PMID:
29915382
PMCID:
PMC6524765

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003934860.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: SPG7 c.1033G>C (p.Ala345Pro) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250854 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1033G>C has been reported in the literature in at least one compound heterozygous individual affected with Hereditary Spastic Paraplegia (e.g., Sun_2019). These data do not allow any conclusion about variant significance. 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: 29915382). Three ClinVar submitters (evaluation after 2014) have cited the variant with conflicting assessments, classifying the variant as VUS (n = 2) or likely pathogenic (n = 1). Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024