rs763659524

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042432.2(CLN3):ā€‹c.283G>Cā€‹(p.Val95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V95I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CLN3
NM_001042432.2 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.19534615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLN3NM_001042432.2 linkuse as main transcriptc.283G>C p.Val95Leu missense_variant 5/16 ENST00000636147.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLN3ENST00000636147.2 linkuse as main transcriptc.283G>C p.Val95Leu missense_variant 5/161 NM_001042432.2 P1Q13286-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251480
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.51
.;D;D;.;T;.;T;D;T;.;T;.;T;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.44
N
LIST_S2
Uncertain
0.86
D;.;.;D;.;T;T;.;D;D;D;D;T;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
1.5
.;L;L;.;.;L;.;L;.;L;.;L;.;.
MutationTaster
Benign
0.88
D;D;D;D;D;D;D;D;D;D;D;D;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.31
.;.;N;.;N;N;.;N;.;N;.;N;.;N
REVEL
Benign
0.26
Sift
Benign
0.44
.;.;T;.;T;T;.;T;.;T;.;T;.;T
Sift4G
Benign
0.69
.;.;.;T;T;T;.;T;.;T;.;T;.;.
Polyphen
0.0090, 0.011, 0.018, 0.031
.;B;B;.;.;.;.;B;.;B;B;B;.;.
Vest4
0.21, 0.20, 0.24, 0.18, 0.27, 0.23
MutPred
0.49
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP
0.74
MPC
0.14
ClinPred
0.12
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.078
gMVP
0.43

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763659524; hg19: chr16-28499923; API