chr16-28486592-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001042432.2(CLN3):c.519T>C(p.Thr173Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,611,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CLN3
NM_001042432.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.13

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronal ceroid lipofuscinosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

CLN3 links:

ENSG00000261832 (HGNC:):

ENSG00000261832 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-28486592-A-G is Benign according to our data. Variant chr16-28486592-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 585707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042432.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CLN3	NM_001042432.2	MANE Select	c.519T>C	p.Thr173Thr	synonymous	Exon 8 of 16	NP_001035897.1
CLN3	NM_000086.2		c.519T>C	p.Thr173Thr	synonymous	Exon 7 of 15	NP_000077.1
CLN3	NM_001286104.2		c.447T>C	p.Thr149Thr	synonymous	Exon 7 of 15	NP_001273033.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CLN3	ENST00000636147.2	TSL:1 MANE Select	c.519T>C	p.Thr173Thr	synonymous	Exon 8 of 16	ENSP00000490105.1
CLN3	ENST00000359984.12	TSL:1	c.519T>C	p.Thr173Thr	synonymous	Exon 7 of 15	ENSP00000353073.9
CLN3	ENST00000565316.6	TSL:1	c.519T>C	p.Thr173Thr	synonymous	Exon 7 of 14	ENSP00000456117.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

244676

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458986

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725522

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33414

American (AMR)

AF:

0.0000226

AC:

AN:

44312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26034

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.00

AC:

AN:

85578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110796

Other (OTH)

AF:

0.0000166

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.000327

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 05, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Neuronal ceroid lipofuscinosis

Benign:1

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.55

(source)

DANN

Benign

0.60

PhyloP100

-2.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over