13-76992025-T-G

Variant names:

• chr13-76992025-T-G
• rs1182554801
• ENST00000636183.2:c.-74T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000636183.2(CLN5):​c.-74T>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 0.00000894 in 1,454,518 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: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CLN5 ENST00000636183.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 0 publications found

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]

CLN5 Gene-Disease associations (from GenCC):

• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health

ENSG00000283208 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16503504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN5	NM_006493.4	c.-74T>G		upstream_gene_variant		ENST00000377453.9	NP_006484.2
CLN5	NM_001366624.2	c.-74T>G		upstream_gene_variant			NP_001353553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000377453.9	c.-74T>G		upstream_gene_variant		1	NM_006493.4	ENSP00000366673.5
ENSG00000283208	ENST00000638147.2	c.-74T>G		upstream_gene_variant		5		ENSP00000490953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000894 AC: 13 AN: 1454518 Hom.: 0 Cov.: 35 AF XY: 0.0000152 AC XY: 11 AN XY: 723254

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1110060

Other (OTH) AF: 0.00 AC: 0 AN: 59982

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.56
PrimateAI	Uncertain	0.59	T
MutPred		0.34		Gain of MoRF binding (P = 0.0025);
ClinPred		0.95	D
GERP RS		-3.2
PromoterAI		-0.011	Neutral

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

Other links and lift over

dbSNP: rs1182554801; hg19: chr13-77566160;