chr16-28477461-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001042432.2(CLN3):​c.*55C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,609,964 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 11 hom. )

Consequence

CLN3
NM_001042432.2 3_prime_UTR

Scores

2
Splicing: ADA: 0.00008658
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.784
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLN3NM_001042432.2 linkuse as main transcriptc.*55C>A 3_prime_UTR_variant 16/16 ENST00000636147.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLN3ENST00000636147.2 linkuse as main transcriptc.*55C>A 3_prime_UTR_variant 16/161 NM_001042432.2 P1Q13286-1

Frequencies

GnomAD3 genomes
AF:
0.000657
AC:
100
AN:
152166
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.0205
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00143
GnomAD4 exome
AF:
0.000706
AC:
1029
AN:
1457680
Hom.:
11
Cov.:
30
AF XY:
0.000723
AC XY:
524
AN XY:
725116
show subpopulations
Gnomad4 AFR exome
AF:
0.000210
Gnomad4 AMR exome
AF:
0.000828
Gnomad4 ASJ exome
AF:
0.0258
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000181
Gnomad4 OTH exome
AF:
0.00168
GnomAD4 genome
AF:
0.000657
AC:
100
AN:
152284
Hom.:
1
Cov.:
32
AF XY:
0.000671
AC XY:
50
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.0205
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000966
Hom.:
0
Bravo
AF:
0.000937
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Neuronal ceroid lipofuscinosis 3 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
17
DANN
Benign
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000087
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.67
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.67
Position offset: 3

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: rs199979207; hg19: chr16-28488782; API