16-28488645-C-G

Variant names:

• chr16-28488645-C-G
• NM_001042432.2:c.240G>C
• CLN3 p.Thr80Thr

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286105.2(CLN3):​c.20G>C​(p.Arg7Pro) variant causes a missense 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. 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. R7C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLN3 NM_001286105.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Myriad Women's Health, G2P, Orphanet

ENSG00000261832 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286105.2. 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.240G>C	p.Thr80Thr	synonymous	Exon 5 of 16	NP_001035897.1	Q13286-1
	CLN3	NM_001286105.2		c.20G>C	p.Arg7Pro	missense	Exon 3 of 13	NP_001273034.1	B4DMY6
	CLN3	NM_000086.2		c.240G>C	p.Thr80Thr	synonymous	Exon 4 of 15	NP_000077.1	Q13286-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN3	ENST00000636147.2	TSL:1 MANE Select	c.240G>C	p.Thr80Thr	synonymous	Exon 5 of 16	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000359984.12	TSL:1	c.240G>C	p.Thr80Thr	synonymous	Exon 4 of 15	ENSP00000353073.9	Q13286-1
	CLN3	ENST00000565316.6	TSL:1	c.240G>C	p.Thr80Thr	synonymous	Exon 4 of 14	ENSP00000456117.1	Q13286-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.10
CADD	Benign	0.042
DANN	Benign	0.92
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.33		Position offset: 17

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

hg19: chr16-28499966;