NM_006493.4:c.78G>C

Variant names:

• chr13-76992176-G-C
• rs104894385
• NM_006493.4:c.78G>C

Variant summary

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

The NM_006493.4(CLN5):​c.78G>C​(p.Trp26Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W26R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLN5 NM_006493.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ENSG00000283208 (HGNC:):

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=0.19649273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN5	NM_006493.4	c.78G>C	p.Trp26Cys	missense_variant	Exon 1 of 4	ENST00000377453.9	NP_006484.2
CLN5	NM_001366624.2	c.78G>C	p.Trp26Cys	missense_variant	Exon 1 of 5		NP_001353553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000377453.9	c.78G>C	p.Trp26Cys	missense_variant	Exon 1 of 4	1	NM_006493.4	ENSP00000366673.5
ENSG00000283208	ENST00000638147.2	c.78G>C	p.Trp26Cys	missense_variant	Exon 1 of 5	5		ENSP00000490953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.67
DEOGEN2	Benign	0.099	T;T;T;T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.61	T;.;T;.;.;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N;.;.;.
PrimateAI	Uncertain	0.70	T
REVEL	Benign	0.096
Polyphen		0.97	.;.;D;.;.;.
MutPred		0.57		.;.;Gain of methylation at R21 (P = 0.0374);.;.;.;
MVP		0.58
MPC		0.28
ClinPred		0.27	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19

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: rs104894385; hg19: chr13-77566311;