rs73533466

Positions:

• chr16-28484025-C-A
• chr16-28484025-C-G
• chr16-28484025-C-T

Variant summary

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

The NM_001042432.2(CLN3):​c.771G>T​(p.Glu257Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E257E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLN3 NM_001042432.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

CLN3 (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=0.19726744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN3	NM_001042432.2	c.771G>T	p.Glu257Asp	missense_variant	10/16	ENST00000636147.2	NP_001035897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN3	ENST00000636147.2	c.771G>T	p.Glu257Asp	missense_variant	10/16	1	NM_001042432.2	ENSP00000490105.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	1.3
DANN	Benign	0.83
DEOGEN2	Uncertain	0.54	.;D;D;.;.;T;.;.;T;D;T;.;T;.;.;.;T;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.79	T;.;.;T;.;.;T;T;T;.;T;T;T;.;T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.4	.;L;L;.;.;.;.;.;.;L;.;L;.;.;.;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.35	.;.;N;.;.;N;N;N;.;N;.;N;.;.;N;.;N;.;N
REVEL	Uncertain	0.34
Sift	Benign	0.23	.;.;T;.;.;T;T;T;.;T;.;T;.;.;T;.;D;.;T
Sift4G	Benign	0.17	.;.;.;T;.;T;T;T;.;T;.;T;.;.;.;.;T;.;.
Polyphen		0.043, 0.49, 0.20, 0.24, 0.73, 0.010	.;B;B;.;.;P;.;.;.;B;P;B;B;.;P;.;B;.;.
Vest4		0.29, 0.31, 0.29, 0.30, 0.30, 0.37
MutPred		0.51		Loss of glycosylation at P259 (P = 0.0891);Loss of glycosylation at P259 (P = 0.0891);Loss of glycosylation at P259 (P = 0.0891);Loss of glycosylation at P259 (P = 0.0891);.;.;.;.;.;Loss of glycosylation at P259 (P = 0.0891);.;Loss of glycosylation at P259 (P = 0.0891);.;.;.;.;.;.;.;
MVP		0.89
MPC		0.23
ClinPred		0.29	T
GERP RS		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.24

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: chr16-28495346;