NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8]) AND multiple conditions

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Oct 26, 2022
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:
RCV001281392.4

Allele description [Variation Report for NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])]

NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])

Gene:
SMPD1:sphingomyelin phosphodiesterase 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000543.5(SMPD1):c.108GCTGGC[8] (p.38AL[8])
HGVS:
  • NC_000011.10:g.6390706GCTGGC[8]
  • NG_011780.1:g.5282GCTGGC[8]
  • NM_000543.4:c.132_143dup12
  • NM_000543.5:c.108GCTGGC[8]MANE SELECT
  • NM_001007593.3:c.108GCTGGC[8]
  • NM_001318087.2:c.108GCTGGC[8]
  • NM_001318088.2:c.-854GCTGGC[8]
  • NM_001365135.2:c.108GCTGGC[8]
  • NP_000534.3:p.38AL[8]
  • NP_001007594.2:p.38AL[8]
  • NP_001305016.1:p.38AL[8]
  • NP_001352064.1:p.38AL[8]
  • NC_000011.9:g.6411935_6411936insGCTGGCGCTGGC
  • NC_000011.9:g.6411936GCTGGC[8]
  • NM_000543.4:c.132_143dup12
  • NM_000543.4:c.132_143dupGCTGGCGCTGGC
  • NM_000543.5:c.132_143dupMANE SELECT
  • NM_000543.5:c.132_143dup12MANE SELECT
  • NR_027400.3:n.233GCTGGC[8]
  • NR_134502.2:n.233GCTGGC[8]
Links:
dbSNP: rs3838786
NCBI 1000 Genomes Browser:
rs3838786
Molecular consequence:
  • NM_001318088.2:c.-854GCTGGC[8] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000543.5:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001007593.3:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001318087.2:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001365135.2:c.108GCTGGC[8] - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NR_027400.3:n.233GCTGGC[8] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_134502.2:n.233GCTGGC[8] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Niemann-Pick disease, type B
Identifiers:
MONDO: MONDO:0011871; MedGen: C0268243; Orphanet: 77293; OMIM: 607616
Name:
Niemann-Pick disease, type A
Synonyms:
SPHINGOMYELIN LIPIDOSIS; SPHINGOMYELINASE DEFICIENCY
Identifiers:
MONDO: MONDO:0009756; MedGen: C0268242; Orphanet: 77292; OMIM: 257200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001468697Huiwen Zhang's lab, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Dec 30, 2020) 		inheritedclinical testing

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

SCV003249670Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 26, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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

Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.

Hu J, Maegawa GHB, Zhan X, Gao X, Wang Y, Xu F, Qiu W, Han L, Gu X, Zhang H.

Hum Mutat. 2021 May;42(5):614-625. doi: 10.1002/humu.24192. Epub 2021 Mar 19.

PubMed [citation]
PMID:
33675270
See all PubMed Citations (3)

Details of each submission

From Huiwen Zhang's lab, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, SCV001468697.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003249670.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant, c.132_143dup, results in the insertion of 4 amino acid(s) of the SMPD1 protein (p.Ala46_Leu49dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with SMPD1-related conditions (PMID: 33675270). ClinVar contains an entry for this variant (Variation ID: 992676). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

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

Last Updated: Sep 29, 2024