Variant 16-28488615-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PM2PP3_ModerateBP6_Very_Strong

The NM_001286105.2(CLN3):c.50T>C(p.Leu17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,614,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CLN3
NM_001286105.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.93

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]

CLN3 links:

CLN3 (HGNC:):

CLN3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

BayesDel_noAF computational evidence supports a deleterious effect, 0.31

BP6

Variant 16-28488615-A-G is Benign according to our data. Variant chr16-28488615-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 205086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-28488615-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN3	NM_001042432.2 linkuse as main transcript	c.270T>C	p.Phe90Phe	synonymous_variant	5/16	ENST00000636147.2	NP_001035897.1	Q13286-1A0A024QZB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN3	ENST00000636147.2 linkuse as main transcript	c.270T>C	p.Phe90Phe	synonymous_variant	5/16	1	NM_001042432.2	ENSP00000490105.1		Q13286-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251486

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.000145

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:

0.000135

AC:

197

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.000134

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:

0.000364

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152316

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00457

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.00137

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2017

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Neuronal ceroid lipofuscinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Pathogenic

0.31

CADD

Benign

DANN

Uncertain

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over