rs386833725

Variant names:

• chr16-28486626-G-A
• NM_001042432.2:c.485C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-28486626-G-A
• chr16-28486626-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001042432.2(CLN3):​c.485C>T​(p.Ser162Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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: CLN3 NM_001042432.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

Genes affected

CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000261832 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN3	NM_001042432.2	c.485C>T	p.Ser162Leu	missense_variant	Exon 8 of 16	ENST00000636147.2	NP_001035897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN3	ENST00000636147.2	c.485C>T	p.Ser162Leu	missense_variant	Exon 8 of 16	1	NM_001042432.2	ENSP00000490105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458698 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725302

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: 9.00e-7

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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.97	.;D;D;.;.;D;.;D;D;.;D;.;.;.;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.;D;.;.;D;.;D;D;D;.;D;D;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.9	.;H;H;.;.;.;.;H;.;H;.;.;H;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.4	.;.;D;.;D;D;D;D;.;D;.;.;D;.;D;.
REVEL	Pathogenic	0.93
Sift	Uncertain	0.0010	.;.;D;.;D;D;D;D;.;D;.;.;D;.;D;.
Sift4G	Uncertain	0.0020	.;.;.;D;.;D;D;D;.;D;.;.;.;.;.;.
Polyphen		1.0, 1.0	.;D;D;.;.;.;.;D;.;D;D;.;D;.;.;.
Vest4		0.88, 0.86, 0.85, 0.87, 0.84
MutPred		0.68		Loss of glycosylation at S162 (P = 0.0262);Loss of glycosylation at S162 (P = 0.0262);Loss of glycosylation at S162 (P = 0.0262);Loss of glycosylation at S162 (P = 0.0262);.;.;.;Loss of glycosylation at S162 (P = 0.0262);.;Loss of glycosylation at S162 (P = 0.0262);.;.;Loss of glycosylation at S162 (P = 0.0262);.;.;.;
MVP		0.98
MPC		0.60
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.93
gMVP		0.84

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: chr16-28497947;