15-68218595-G-T

Variant names:

• chr15-68218595-G-T
• NM_017882.3:c.139C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017882.3(CLN6):​c.139C>A​(p.Leu47Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000048 (0 hom.)
• Consequence: CLN6 NM_017882.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42

Genes affected

CLN6 (HGNC:2077): (CLN6 transmembrane ER 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]

ENSG00000260007 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN6	NM_017882.3	c.139C>A	p.Leu47Ile	missense_variant	Exon 2 of 7	ENST00000249806.11	NP_060352.1
CLN6	NM_001411068.1	c.235C>A	p.Leu79Ile	missense_variant	Exon 2 of 7		NP_001397997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN6	ENST00000249806.11	c.139C>A	p.Leu47Ile	missense_variant	Exon 2 of 7	1	NM_017882.3	ENSP00000249806.5
ENSG00000260007	ENST00000562767.2	c.83+10907C>A		intron_variant	Intron 1 of 2	3		ENSP00000456336.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727178

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;D;.;T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;.;.;N
REVEL	Pathogenic	0.74
Sift	Uncertain	0.022	D;D;D;.;.;D
Sift4G	Uncertain	0.037	D;D;D;.;.;D
Polyphen		0.97	D;.;.;.;.;.
Vest4		0.65
MutPred		0.37		.;.;Loss of helix (P = 0.1706);.;.;.;
MVP		0.92
MPC		1.1
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.28
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-68510933;