rs386833738

Variant names:

• chr16-28484003-T-A
• rs386833738
• NM_001042432.2:c.790+3A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-28484003-T-A
• chr16-28484003-T-C
• chr16-28484003-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001042432.2(CLN3):​c.790+3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLN3 NM_001042432.2 splice_region, intron
• Scores: Splicing: ADA: 0.9952
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 0 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: Ambry Genetics, Genomics England PanelApp, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000261832 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. Scorers claiming Benign: dbscSNV1_RF.

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.790+3A>T		splice_region intron	N/A	NP_001035897.1	Q13286-1
	CLN3	NM_000086.2		c.790+3A>T		splice_region intron	N/A	NP_000077.1	Q13286-1
	CLN3	NM_001286104.2		c.718+3A>T		splice_region 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.790+3A>T		splice_region intron	N/A	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000359984.12	TSL:1	c.790+3A>T		splice_region intron	N/A	ENSP00000353073.9	Q13286-1
	CLN3	ENST00000565316.6	TSL:1	c.790+3A>T		splice_region intron	N/A	ENSP00000456117.1	Q13286-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	33
DANN	Benign	0.89
PhyloP100		-0.059

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.72
SpliceAI score (max)		0.81		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.81		Position offset: -22

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

Other links and lift over

dbSNP: rs386833738; hg19: chr16-28495324;