16-28479196-T-C

Variant names:

• chr16-28479196-T-C
• rs151181
• NM_001042432.2:c.1057-1319A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042432.2(CLN3):​c.1057-1319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,140 control chromosomes in the GnomAD database, including 9,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9292 hom., cov: 32)
• Consequence: CLN3 NM_001042432.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 84 publications found

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: G2P, Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women's Health

ENSG00000261832 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN3	NM_001042432.2	MANE Select	c.1057-1319A>G		intron	N/A	NP_001035897.1	Q13286-1
	CLN3	NM_000086.2		c.1057-1319A>G		intron	N/A	NP_000077.1	Q13286-1
	CLN3	NM_001286104.2		c.985-1319A>G		intron	N/A	NP_001273033.1	Q13286-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN3	ENST00000636147.2	TSL:1 MANE Select	c.1057-1319A>G		intron	N/A	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000359984.12	TSL:1	c.1057-1319A>G		intron	N/A	ENSP00000353073.9	Q13286-1
	CLN3	ENST00000565316.6	TSL:1	c.1006-1319A>G		intron	N/A	ENSP00000456117.1	Q13286-3

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49076 AN: 152022 Hom.: 9281 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49127 AN: 152140 Hom.: 9292 Cov.: 32 AF XY: 0.323 AC XY: 24014 AN XY: 74356

African (AFR) AF: 0.158 AC: 6576 AN: 41536

American (AMR) AF: 0.401 AC: 6130 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5178

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4824

European-Finnish (FIN) AF: 0.482 AC: 5090 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27789 AN: 67980

Other (OTH) AF: 0.305 AC: 642 AN: 2108

Alfa AF: 0.371 Hom.: 41644

Bravo AF: 0.310

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs151181;

hg19: chr16-28490517;