NM_001077418.3(TMEM231):c.664+4A>G AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Dec 9, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000650603.2

Allele description [Variation Report for NM_001077418.3(TMEM231):c.664+4A>G]

NM_001077418.3(TMEM231):c.664+4A>G

Gene:
TMEM231:transmembrane protein 231 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q23.1
Genomic location:
Preferred name:
NM_001077418.3(TMEM231):c.664+4A>G
HGVS:
  • NC_000016.10:g.75542598T>C
  • NG_033109.1:g.18689A>G
  • NM_001077416.2:c.823+4A>G
  • NM_001077418.3:c.664+4A>GMANE SELECT
  • NC_000016.9:g.75576496T>C
  • NM_001077418.1:c.664+4A>G
Links:
dbSNP: rs760426025
NCBI 1000 Genomes Browser:
rs760426025
Molecular consequence:
  • NM_001077416.2:c.823+4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001077418.3:c.664+4A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Joubert syndrome 20 (JBTS20)
Identifiers:
MONDO: MONDO:0013994; MedGen: C3554235; Orphanet: 475; OMIM: 614970
Name:
Meckel syndrome, type 11 (MKS11)
Identifiers:
MONDO: MONDO:0014164; MedGen: C3809352; Orphanet: 564; OMIM: 615397

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000772450Invitaecriteria provided, single submitter
Pathogenic
(Dec 9, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone.

Roberson EC, Dowdle WE, Ozanturk A, Garcia-Gonzalo FR, Li C, Halbritter J, Elkhartoufi N, Porath JD, Cope H, Ashley-Koch A, Gregory S, Thomas S, Sayer JA, Saunier S, Otto EA, Katsanis N, Davis EE, AttiƩ-Bitach T, Hildebrandt F, Leroux MR, Reiter JF.

J Cell Biol. 2015 Apr 13;209(1):129-42. doi: 10.1083/jcb.201411087.

PubMed [citation]
PMID:
25869670
PMCID:
PMC4395494

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000772450.2

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

Description

This sequence change falls in intron 4 of the TMEM231 gene. It does not directly change the encoded amino acid sequence of the TMEM231 protein, but it affects a nucleotide within the consensus splice site of the intron. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed as homozygous or on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with Meckel syndrome (PMID: 25869670). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 437009). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this change alters splicing leading to premature truncation (PMID: 25869670). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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