NM_001382391.1(CSPP1):c.3292C>T (p.Arg1098Trp) AND Joubert syndrome 21

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 27, 2022
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:: RCV001332557.5

Allele description [Variation Report for NM_001382391.1(CSPP1):c.3292C>T (p.Arg1098Trp)]

NM_001382391.1(CSPP1):c.3292C>T (p.Arg1098Trp)

Genes:

ARFGEF1:ARF guanine nucleotide exchange factor 1 [Gene - OMIM - HGNC]
CSPP1:centrosome and spindle pole associated protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q13.2

Genomic location:

Preferred name:

NM_001382391.1(CSPP1):c.3292C>T (p.Arg1098Trp)

HGVS:

NC_000008.11:g.67190721C>T
NG_034100.1:g.131354C>T
NM_001291339.2:c.2242C>T
NM_001363131.2:c.3211C>T
NM_001363132.2:c.3097C>T
NM_001363133.2:c.3016C>T
NM_001364869.1:c.3358C>T
NM_001364870.1:c.3178C>T
NM_001382391.1:c.3292C>TMANE SELECT
NM_024790.6:c.3277C>T
NP_001278268.1:p.Arg748Trp
NP_001350060.1:p.Arg1071Trp
NP_001350061.1:p.Arg1033Trp
NP_001350062.1:p.Arg1006Trp
NP_001351798.1:p.Arg1120Trp
NP_001351799.1:p.Arg1060Trp
NP_001369320.1:p.Arg1098Trp
NP_079066.5:p.Arg1093Trp
NC_000008.10:g.68102956C>T

Protein change:

R1006W

Links:

dbSNP: rs759630451

NCBI 1000 Genomes Browser:

rs759630451

Molecular consequence:

NM_001291339.2:c.2242C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363131.2:c.3211C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363132.2:c.3097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363133.2:c.3016C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364869.1:c.3358C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364870.1:c.3178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382391.1:c.3292C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024790.6:c.3277C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Joubert syndrome 21 (JBTS21)
Identifiers:: MONDO: MONDO:0014288; MedGen: C3810212; OMIM: 615636

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001524923	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 12, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002186693	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2022)	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

SCV001524923

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 12, 2019)

unknown

clinical testing

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

SCV002186693

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 2022)

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
not provided	unknown	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

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 Baylor Genetics, SCV001524923.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002186693.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1030874). This variant has not been reported in the literature in individuals affected with CSPP1-related conditions. This variant is present in population databases (rs759630451, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1093 of the CSPP1 protein (p.Arg1093Trp).

#	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: Sep 29, 2024

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