NM_014780.4(CUL7):c.3041T>G (p.Leu1014Arg) AND Three M syndrome 1

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Dec 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000755718.2

Allele description [Variation Report for NM_014780.4(CUL7):c.3041T>G (p.Leu1014Arg)]

NM_014780.4(CUL7):c.3041T>G (p.Leu1014Arg)

Gene:
CUL7:cullin 7 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.1
Genomic location:
Preferred name:
NM_014780.4(CUL7):c.3041T>G (p.Leu1014Arg)
HGVS:
  • NC_000006.12:g.43044883A>C
  • NG_016205.1:g.14063T>G
  • NM_001168370.1:c.3293T>G
  • NM_014780.4:c.3041T>G
  • NP_001161842.1:p.Leu1098Arg
  • NP_055595.2:p.Leu1014Arg
  • NC_000006.11:g.43012621A>C
  • Q14999:p.Leu1014Arg
Protein change:
L1014R
Links:
UniProtKB: Q14999#VAR_026122; dbSNP: rs61752334
NCBI 1000 Genomes Browser:
rs61752334
Molecular consequence:
  • NM_001168370.1:c.3293T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014780.4:c.3041T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Three M syndrome 1 (3M1)
Synonyms:
GLOOMY FACE SYNDROME; 3M SYNDROME; 3M syndrome 1
Identifiers:
MONDO: MONDO:0010117; MedGen: C1848862; Orphanet: 2616; OMIM: 273750

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000883195SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Uncertain significance
(Oct 15, 2018)
unknowncuration

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

SCV001369347Centre for Mendelian Genomics,University Medical Centre Ljubljanacriteria provided, single submitter
Likely pathogenic
(Dec 12, 2019)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Identification of mutations in CUL7 in 3-M syndrome.

Huber C, Dias-Santagata D, Glaser A, O'Sullivan J, Brauner R, Wu K, Xu X, Pearce K, Wang R, Uzielli ML, Dagoneau N, Chemaitilly W, Superti-Furga A, Dos Santos H, Mégarbané A, Morin G, Gillessen-Kaesbach G, Hennekam R, Van der Burgt I, Black GC, Clayton PE, Read A, et al.

Nat Genet. 2005 Oct;37(10):1119-24. Epub 2005 Sep 4.

PubMed [citation]
PMID:
16142236

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

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000883195.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Three M syndrome 1, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM3-Supporting => PM3 downgraded in strength to Supporting (https://www.ncbi.nlm.nih.gov/pubmed/16142236).

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

From Centre for Mendelian Genomics,University Medical Centre Ljubljana, SCV001369347.2

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

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3. This variant was detected in homozygous state.

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

Last Updated: Sep 7, 2021

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