Variant 16-28482128-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001042432.2(CLN3):c.1033A>C(p.Thr345Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T345S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CLN3
NM_001042432.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a topological_domain Lumenal (size 47) in uniprot entity CLN3_HUMAN there are 12 pathogenic changes around while only 2 benign (86%) in NM_001042432.2

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLN3	NM_001042432.2 linkuse as main transcript	c.1033A>C	p.Thr345Pro	missense_variant	14/16	ENST00000636147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLN3	ENST00000636147.2 linkuse as main transcript	c.1033A>C	p.Thr345Pro	missense_variant	14/16	1	NM_001042432.2	P1	Q13286-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248462

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134442

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461214

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726866

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

.;.;D;D;.;D;.;.;D;D;D;.;D;.;.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.89

D;D;.;.;.;.;D;D;D;.;D;D;D;.;D;D;D

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.45

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.5

.;.;M;M;.;.;.;.;.;M;.;.;.;.;.;.;.

MutationTaster

Benign

0.82

D;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

.;.;.;D;.;D;D;N;.;D;.;N;.;.;N;.;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

.;.;.;D;.;D;D;D;.;D;.;D;.;.;D;.;.

Sift4G

Uncertain

0.0030

.;.;.;.;.;D;D;D;.;D;.;D;.;.;.;.;.

Polyphen

0.98, 0.056, 0.99, 1.0

.;.;D;D;.;B;.;.;.;D;B;D;D;.;D;.;.

Vest4

0.68, 0.65, 0.67, 0.68, 0.67

MVP

0.79

MPC

0.65

ClinPred

0.90

GERP RS

5.2

Varity_R

0.88

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over