Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000636147.2(CLN3):āc.313A>Gā(p.Ile105Val) variant causes a missense change. The variant allele was found at a frequency of 0.00314 in 1,613,650 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I105F) has been classified as Uncertain significance.
CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
Computational evidence support a benign effect (MetaRNN=0.012943447).
BP6
Variant 16-28487723-T-C is Benign according to our data. Variant chr16-28487723-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 128777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-28487723-T-C is described in Lovd as [Likely_benign].
BA1
GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.
Genetic Services Laboratory, University of Chicago
-
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter
clinical testing
GeneDx
May 10, 2012
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter
clinical testing
Eurofins Ntd Llc (ga)
Apr 07, 2014
- -
Benign, criteria provided, single submitter
clinical testing
Athena Diagnostics
Mar 10, 2020
- -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Mar 14, 2016
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
Likely benign, criteria provided, single submitter
Likely benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jun 14, 2016
- -
Neuronal ceroid lipofuscinosis Benign:1
Benign, criteria provided, single submitter
clinical testing
Labcorp Genetics (formerly Invitae), Labcorp
Feb 01, 2024
- -
Neuronal ceroid lipofuscinosis 3 Benign:1
Benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jan 12, 2018
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -