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NM_153704.6(TMEM67):c.329A>T (p.Asp110Val) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 17, 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:
RCV003026877.3

Allele description [Variation Report for NM_153704.6(TMEM67):c.329A>T (p.Asp110Val)]

NM_153704.6(TMEM67):c.329A>T (p.Asp110Val)

Gene:
TMEM67:transmembrane protein 67 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q22.1
Genomic location:
Preferred name:
NM_153704.6(TMEM67):c.329A>T (p.Asp110Val)
HGVS:
  • NC_000008.11:g.93758499A>T
  • NG_009190.1:g.8656A>T
  • NM_001142301.1:c.-49A>T
  • NM_153704.6:c.329A>TMANE SELECT
  • NP_714915.3:p.Asp110Val
  • NP_714915.3:p.Asp110Val
  • LRG_688t1:c.329A>T
  • LRG_688t2:c.-49A>T
  • LRG_688:g.8656A>T
  • LRG_688p1:p.Asp110Val
  • NC_000008.10:g.94770727A>T
  • NM_153704.5:c.329A>T
  • NR_024522.2:n.350A>T
Protein change:
D110V
Molecular consequence:
  • NM_001142301.1:c.-49A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_153704.6:c.329A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_024522.2:n.350A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial aplasia of the vermis
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300
Name:
Meckel-Gruber syndrome
Synonyms:
DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:
MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003328339Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 17, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The diagnostic utility of exome sequencing in Joubert syndrome and related disorders.

Tsurusaki Y, Kobayashi Y, Hisano M, Ito S, Doi H, Nakashima M, Saitsu H, Matsumoto N, Miyake N.

J Hum Genet. 2013 Feb;58(2):113-5. doi: 10.1038/jhg.2012.117. Epub 2012 Oct 4. Erratum in: J Hum Genet. 2015 Oct;60(10):651. doi: 10.1038/jhg.2015.86.

PubMed [citation]
PMID:
23034536

Neuroimaging findings in Joubert syndrome with C5orf42 gene mutations: A milder form of molar tooth sign and vermian hypoplasia.

Enokizono M, Aida N, Niwa T, Osaka H, Naruto T, Kurosawa K, Ohba C, Suzuki T, Saitsu H, Goto T, Matsumoto N.

J Neurol Sci. 2017 May 15;376:7-12. doi: 10.1016/j.jns.2017.02.065. Epub 2017 Mar 1.

PubMed [citation]
PMID:
28431631
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003328339.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TMEM67 protein function. ClinVar contains an entry for this variant (Variation ID: 2112541). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 110 of the TMEM67 protein (p.Asp110Val). This variant disrupts the p.Asp110 amino acid residue in TMEM67. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23034536, 28431631). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024