rs587780896

Positions:

• chr13-76992095-C-G
• chr13-76992095-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006493.4(CLN5):​c.-4C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CLN5 NM_006493.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15108514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN5	NM_006493.4	c.-4C>G		5_prime_UTR_variant	1/4	ENST00000377453.9	NP_006484.2
CLN5	NM_001366624.2	c.-4C>G		5_prime_UTR_variant	1/5		NP_001353553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000377453.9	c.-4C>G		5_prime_UTR_variant	1/4	1	NM_006493.4	ENSP00000366673	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000852 AC: 2 AN: 234874 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129382

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000196

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459560 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;T;T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.34	T;.;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
MutPred		0.30		Gain of catalytic residue at S44 (P = 0.0016);.;.;.;
ClinPred		0.93	D
GERP RS		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587780896; hg19: chr13-77566230;