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NM_006493.4(CLN5):c.61C>T (p.Arg21Trp) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jul 1, 2016
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:
RCV000187066.4

Allele description [Variation Report for NM_006493.4(CLN5):c.61C>T (p.Arg21Trp)]

NM_006493.4(CLN5):c.61C>T (p.Arg21Trp)

Genes:
LOC130009913:ATAC-STARR-seq lymphoblastoid silent region 5414 [Gene]
CLN5:CLN5 intracellular trafficking protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q22.3
Genomic location:
Preferred name:
NM_006493.4(CLN5):c.61C>T (p.Arg21Trp)
Other names:
p.R70W:CGG>TGG
HGVS:
  • NC_000013.11:g.76992159C>T
  • NG_009064.1:g.5236C>T
  • NM_001366624.2:c.61C>T
  • NM_006493.4:c.61C>TMANE SELECT
  • NP_001353553.1:p.Arg21Trp
  • NP_006484.2:p.Arg21Trp
  • LRG_692t1:c.208C>T
  • LRG_692:g.5236C>T
  • NC_000013.10:g.77566294C>T
  • NM_006493.2:c.208C>T
Protein change:
R21W
Links:
dbSNP: rs376454715
NCBI 1000 Genomes Browser:
rs376454715
Molecular consequence:
  • NM_001366624.2:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006493.4:c.61C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000240641GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Jul 1, 2016) 		germlineclinical testing

Citation Link,

SCV001553784Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Uncertain significanceunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000240641.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R70W variant has not been publishedas a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R70W variant was notobserved with any significant frequency in approximately 6,200 individuals of European and African Americanancestry in the NHLBI Exome Sequencing Project, but the 1000 Genomes Project reports it was observed in 2/978(0.2%) alleles from individuals of South Asian background. The R70W variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, sizeand/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore,based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benignvariant.

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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001553784.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CLN5 p.R21W variant was not identified in the literature but was identified in dbSNP (ID: rs376454715) and ClinVar (classified as uncertain significance by Invitae, GeneDx and Illumina). The variant was identified in control databases in 26 of 222450 chromosomes at a frequency of 0.0001169 (Genome Aggregation Database March 6, 2019, v2.1.1). The pR21 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: May 1, 2024