NM_003590.5(CUL3):c.1549_1552del (p.Ser517fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001171551.2

Allele description [Variation Report for NM_003590.5(CUL3):c.1549_1552del (p.Ser517fs)]

NM_003590.5(CUL3):c.1549_1552del (p.Ser517fs)

Gene:

CUL3:cullin 3 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2q36.2

Genomic location:

Preferred name:

NM_003590.5(CUL3):c.1549_1552del (p.Ser517fs)

HGVS:

NC_000002.12:g.224500421CTGA[1]
NC_000002.12:g.224500421_224500424CTGA[1]
NG_032169.1:g.89970TCAG[1]
NM_001257197.2:c.1351_1354del
NM_001257198.2:c.1567_1570del
NM_003590.5:c.1549_1552delMANE SELECT
NP_001244126.1:p.Ser451fs
NP_001244127.1:p.Ser523fs
NP_003581.1:p.Ser517fs
NC_000002.11:g.225365138CTGA[1]
NC_000002.11:g.225365138_225365141del
NM_001257198.1:c.1567_1570del
NM_003590.4:c.1549_1552del

Protein change:

S451fs

Links:

dbSNP: rs1692335353

NCBI 1000 Genomes Browser:

rs1692335353

Molecular consequence:

NM_001257197.2:c.1351_1354del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257198.2:c.1567_1570del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003590.5:c.1549_1552del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001334339	Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 12, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004633818	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 21, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32341456, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001334339

Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 12, 2019)

germline

clinical testing

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

SCV004633818

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 21, 2023)

germline

clinical testing

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

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.

Nakashima M, Kato M, Matsukura M, Kira R, Ngu LH, Lichtenbelt KD, van Gassen KLI, Mitsuhashi S, Saitsu H, Matsumoto N.

J Hum Genet. 2020 Sep;65(9):727-734. doi: 10.1038/s10038-020-0758-2. Epub 2020 Apr 27.

PubMed [citation]

PMID:: 32341456

See all PubMed Citations (3)

Details of each submission

From Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes, SCV001334339.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004633818.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ser517Profs*23) in the CUL3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CUL3 are known to be pathogenic (PMID: 32341456). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CUL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 916050). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2024

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