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NM_153704.6(TMEM67):c.395G>C (p.Gly132Ala) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 14, 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:
RCV003230855.1

Allele description [Variation Report for NM_153704.6(TMEM67):c.395G>C (p.Gly132Ala)]

NM_153704.6(TMEM67):c.395G>C (p.Gly132Ala)

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.395G>C (p.Gly132Ala)
HGVS:
  • NC_000008.11:g.93758565G>C
  • NG_009190.1:g.8722G>C
  • NM_001142301.1:c.18G>C
  • NM_153704.6:c.395G>CMANE SELECT
  • NP_001135773.1:p.Trp6Cys
  • NP_714915.3:p.Gly132Ala
  • NP_714915.3:p.Gly132Ala
  • LRG_688t1:c.395G>C
  • LRG_688t2:c.18G>C
  • LRG_688:g.8722G>C
  • LRG_688p1:p.Gly132Ala
  • LRG_688p2:p.Trp6Cys
  • NC_000008.10:g.94770793G>C
  • NM_153704.5:c.395G>C
  • NR_024522.2:n.416G>C
Protein change:
G132A
Molecular consequence:
  • NM_001142301.1:c.18G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153704.6:c.395G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_024522.2:n.416G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003928718Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Apr 14, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Molecular genetic analysis of 30 families with Joubert syndrome.

Suzuki T, Miyake N, Tsurusaki Y, Okamoto N, Alkindy A, Inaba A, Sato M, Ito S, Muramatsu K, Kimura S, Ieda D, Saitoh S, Hiyane M, Suzumura H, Yagyu K, Shiraishi H, Nakajima M, Fueki N, Habata Y, Ueda Y, Komatsu Y, Yan K, et al.

Clin Genet. 2016 Dec;90(6):526-535. doi: 10.1111/cge.12836. Epub 2016 Sep 26.

PubMed [citation]
PMID:
27434533

Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.

Lee SH, Nam TS, Li W, Kim JH, Yoon W, Choi YD, Kim KH, Cai H, Kim MJ, Kim C, Choy HE, Kim N, Chay KO, Kim MK, Choi SY.

Sci Rep. 2017 Aug 31;7(1):10222. doi: 10.1038/s41598-017-10652-z.

PubMed [citation]
PMID:
28860541
PMCID:
PMC5579020

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003928718.1

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

Description

Variant summary: TMEM67 c.395G>C (p.Gly132Ala) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251392 control chromosomes (gnomAD). c.395G>C has been reported in the literature in the compound heterozygous state in an individual affected with Joubert Syndrome and in an individual affected with COACH syndrome (Suzuki_2016, Lee_2017). These data indicate that the variant may be associated with disease. A publication evaluating an impact of the variant in a zebrafish model found that the variant was unable to rescue a hydrocephalus phenotype, however, does not allow strong conclusions about the magnitude of variant effect on protein function versus the WT (Lee_2017). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Jun 10, 2023