rs9565309

chr13-77002892-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006493.4(CLN5):c.*1923T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,274 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (217 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CLN5 NM_006493.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

Genes affected

CLN5 (HGNC:2076): (CLN5 intracellular trafficking protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function.[provided by RefSeq, Oct 2008]

FBXL3 (HGNC:13599): (F-box and leucine rich repeat protein 3) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats and is localized in the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLN5	NM_006493.4	c.*1923T>C		3_prime_UTR_variant	4/4	ENST00000377453.9
CLN5	NM_001366624.2	c.*2449T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLN5	ENST00000377453.9	c.*1923T>C		3_prime_UTR_variant	4/4	1	NM_006493.4	P1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5730 AN: 152156 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0321

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0377 AC: 5738 AN: 152274 Hom.: 217 Cov.: 32 AF XY: 0.0401 AC XY: 2983 AN XY: 74466

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0384 Hom.: 162

Bravo AF: 0.0421

Asia WGS AF: 0.0950 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.2
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9565309; hg19: chr13-77577027;