NM_153704.6(TMEM67):c.224G>A (p.Gly75Glu) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV000472800.8

Allele description

NM_153704.6(TMEM67):c.224G>A (p.Gly75Glu)

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.224G>A (p.Gly75Glu)

HGVS:

NC_000008.11:g.93755778G>A
NG_009190.1:g.5935G>A
NM_001142301.1:c.-62+641G>A
NM_153704.6:c.224G>AMANE SELECT
NP_714915.3:p.Gly75Glu
NP_714915.3:p.Gly75Glu
LRG_688t1:c.224G>A
LRG_688t2:c.-62+641G>A
LRG_688:g.5935G>A
LRG_688p1:p.Gly75Glu
NC_000008.10:g.94768006G>A
NM_153704.5:c.224G>A
NR_024522.2:n.245G>A

Protein change:

G75E

Links:

dbSNP: rs780823805

NCBI 1000 Genomes Browser:

rs780823805

Molecular consequence:

NM_001142301.1:c.-62+641G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_153704.6:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_024522.2:n.245G>A - 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

Recent activity

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Mus musculus katanin p60 subunit A-like 2 (Katnal2), transcript variant 2, mRNA
Mus musculus katanin p60 subunit A-like 2 (Katnal2), transcript variant 2, mRNA
gi|1573307406|ref|NM_001368656.1|

Nucleotide
Mus musculus katanin p60 subunit A-like 2 (Katnal2), transcript variant 3, mRNA
Mus musculus katanin p60 subunit A-like 2 (Katnal2), transcript variant 3, mRNA
gi|1573307372|ref|NM_001368657.1|

Nucleotide
Chain B, Acetyl-CoA acetyltransferase
Chain B, Acetyl-CoA acetyltransferase
gi|49258383|pdb|1OU6|B

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552809	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	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

SCV000552809

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

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	unknown	not provided	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

Details of each submission

From Invitae, SCV000552809.7

#	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 glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 75 of the TMEM67 protein (p.Gly75Glu). This variant is present in population databases (rs780823805, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 411582). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

Last Updated: May 1, 2024

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