Genetic Variant CLN5:c.-83G>C (chr13-76992016-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000636183.2(CLN5):c.-83G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,082 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: 6.9e-7 ( 0 hom. )

Consequence

CLN5
ENST00000636183.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.487

Publications

0 publications found

Variant links:

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

CLN5 links:

ENSG00000283208 (HGNC:):

ENSG00000283208 links:

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ACMG classification

Classification was made for transcript

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=0.2057975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636183.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN5	NM_006493.4	MANE Select	c.-83G>C		upstream_gene	N/A	NP_006484.2
	CLN5	NM_001366624.2		c.-83G>C		upstream_gene	N/A	NP_001353553.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLN5	ENST00000636183.2	TSL:1	c.-83G>C	5_prime_UTR	Exon 1 of 4	ENSP00000490181.2
CLN5	ENST00000377453.9	TSL:1 MANE Select	c.-83G>C	upstream_gene	N/A	ENSP00000366673.5
ENSG00000283208	ENST00000638147.2	TSL:5	c.-83G>C	upstream_gene	N/A	ENSP00000490953.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25938

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.00

AC:

AN:

85528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110042

Other (OTH)

AF:

0.00

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.069

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.28

M_CAP

Benign

0.0013

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

PhyloP100

-0.49

PrimateAI

Uncertain

0.60

MutPred

0.40

Gain of catalytic residue at P21 (P = 8e-04)

ClinPred

0.75

GERP RS

-4.2

PromoterAI

0.31

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over