rs1555468634

Variant names:

• chr16-28485964-GATTGCAATCATAATCAAGTTTTCTTTTCTTTCTTTTTTTTTTTTTCTTCCTGAGACAGAGTCTAACTCTGTCGCCCGGGCTGGAGTGCAATGGCACGATCTCGGCTCACTGCCACCACTGCCTCCGGGGTTCAAGCGATTCTCCTGCCTTAGCCTCCTGAGTAGTTGGGACTACAGGCACCCGCCACCACACCTGGCTAATTGTTGTATTTTTAGTAGAGACGGGGTTTCACCATGTTGGCCAGGCTGGTTTCCTGACCTTAGGCGATCTGCCCTCCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCACACCCAGCCATGGCCAAGTTTTCTCTCCTTGGACCCCTCTCCCTCCCGGCTCAGGGCAGCTCACCTGGCCAGCAGCAGGGCAGGGATACCCAGCATGGACAGCAGGGTCTGCTGAGGGGAGAGGCCGGCCTGGGTGAGGCCCAGGTAGGACAGGGCCCCCAGCAGCCCAGCTCCCCCAGTCCCTGAGGACCACCAGGAGATCACGGCCCTGGGAAGGAGAACACAGGAACATTCAGGAGGACCTAGGCTGACCATGGGACAGCCTCTCCCCACACTCCCTGCTCCACCTGCTTACCTGGGGTAGAAGGCAGTGAGGGAGAGGAAGGTGACCTCCCCAAGGCCTGATGAGATGCTAGCGAAGACCACACCTGGGGGGAGGACAAGCACTGGGATGGTCACACCACACCTTGCCACACTGCCCAGGCCTCTAATGTGTCTGGCCATGGCCTCCTCAGTATCAGCTCATAGAGGCTCCAATAGATCCCATGCATAGGCCAGGTTCCAGGTCTGAAGCAGAGCCCCACTCCCCTGCGTGTCCCTTCATGGAGAGTGGCACCTCCATCCACCCAGTTATCAGACCAGGGGCAGACATGCACCCTTGATGTCTCTGCCCCTTCATCAGTCTTTTTCTTTTCTTTTCTTTTTGGA-G
• rs1555468634
• NM_001042432.2:c.461-280_677+382del

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PP5_Very_Strong

The NM_001042432.2(CLN3):​c.461-280_677+382del variant causes a exon loss change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLN3 NM_001042432.2 exon_loss
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:4 O:1
• Conservation: PhyloP100: 1.07
• Publications: 6 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: Likely_pathogenic. The variant received 8 ACMG points.

• PP5: Variant 16-28485964-GATTGCAATCATAATCAAGTTTTCTTTTCTTTCTTTTTTTTTTTTTCTTCCTGAGACAGAGTCTAACTCTGTCGCCCGGGCTGGAGTGCAATGGCACGATCTCGGCTCACTGCCACCACTGCCTCCGGGGTTCAAGCGATTCTCCTGCCTTAGCCTCCTGAGTAGTTGGGACTACAGGCACCCGCCACCACACCTGGCTAATTGTTGTATTTTTAGTAGAGACGGGGTTTCACCATGTTGGCCAGGCTGGTTTCCTGACCTTAGGCGATCTGCCCTCCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCACACCCAGCCATGGCCAAGTTTTCTCTCCTTGGACCCCTCTCCCTCCCGGCTCAGGGCAGCTCACCTGGCCAGCAGCAGGGCAGGGATACCCAGCATGGACAGCAGGGTCTGCTGAGGGGAGAGGCCGGCCTGGGTGAGGCCCAGGTAGGACAGGGCCCCCAGCAGCCCAGCTCCCCCAGTCCCTGAGGACCACCAGGAGATCACGGCCCTGGGAAGGAGAACACAGGAACATTCAGGAGGACCTAGGCTGACCATGGGACAGCCTCTCCCCACACTCCCTGCTCCACCTGCTTACCTGGGGTAGAAGGCAGTGAGGGAGAGGAAGGTGACCTCCCCAAGGCCTGATGAGATGCTAGCGAAGACCACACCTGGGGGGAGGACAAGCACTGGGATGGTCACACCACACCTTGCCACACTGCCCAGGCCTCTAATGTGTCTGGCCATGGCCTCCTCAGTATCAGCTCATAGAGGCTCCAATAGATCCCATGCATAGGCCAGGTTCCAGGTCTGAAGCAGAGCCCCACTCCCCTGCGTGTCCCTTCATGGAGAGTGGCACCTCCATCCACCCAGTTATCAGACCAGGGGCAGACATGCACCCTTGATGTCTCTGCCCCTTCATCAGTCTTTTTCTTTTCTTTTCTTTTTGGA-G is Pathogenic according to our data. Variant chr16-28485964-GATTGCAATCATAATCAAGTTTTCTTTTCTTTCTTTTTTTTTTTTTCTTCCTGAGACAGAGTCTAACTCTGTCGCCCGGGCTGGAGTGCAATGGCACGATCTCGGCTCACTGCCACCACTGCCTCCGGGGTTCAAGCGATTCTCCTGCCTTAGCCTCCTGAGTAGTTGGGACTACAGGCACCCGCCACCACACCTGGCTAATTGTTGTATTTTTAGTAGAGACGGGGTTTCACCATGTTGGCCAGGCTGGTTTCCTGACCTTAGGCGATCTGCCCTCCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCACACCCAGCCATGGCCAAGTTTTCTCTCCTTGGACCCCTCTCCCTCCCGGCTCAGGGCAGCTCACCTGGCCAGCAGCAGGGCAGGGATACCCAGCATGGACAGCAGGGTCTGCTGAGGGGAGAGGCCGGCCTGGGTGAGGCCCAGGTAGGACAGGGCCCCCAGCAGCCCAGCTCCCCCAGTCCCTGAGGACCACCAGGAGATCACGGCCCTGGGAAGGAGAACACAGGAACATTCAGGAGGACCTAGGCTGACCATGGGACAGCCTCTCCCCACACTCCCTGCTCCACCTGCTTACCTGGGGTAGAAGGCAGTGAGGGAGAGGAAGGTGACCTCCCCAAGGCCTGATGAGATGCTAGCGAAGACCACACCTGGGGGGAGGACAAGCACTGGGATGGTCACACCACACCTTGCCACACTGCCCAGGCCTCTAATGTGTCTGGCCATGGCCTCCTCAGTATCAGCTCATAGAGGCTCCAATAGATCCCATGCATAGGCCAGGTTCCAGGTCTGAAGCAGAGCCCCACTCCCCTGCGTGTCCCTTCATGGAGAGTGGCACCTCCATCCACCCAGTTATCAGACCAGGGGCAGACATGCACCCTTGATGTCTCTGCCCCTTCATCAGTCTTTTTCTTTTCTTTTCTTTTTGGA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 3552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.461-280_677+382del		exon_loss	Exon 9 of 16	NP_001035897.1	Q13286-1
	CLN3	NM_001042432.2	MANE Select	c.461-280_677+382del		exon_loss	Exon 8 of 16	NP_001035897.1	Q13286-1
	CLN3	NM_000086.2		c.461-280_677+382del		exon_loss	Exon 8 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.461-280_677+382del		exon_loss	Exon 8 of 16	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000636147.2	TSL:1 MANE Select	c.461-280_677+382del		exon_loss	Exon 9 of 16	ENSP00000490105.1	Q13286-1
	CLN3	ENST00000359984.12	TSL:1	c.461-280_677+382del		exon_loss	Exon 7 of 15	ENSP00000353073.9	Q13286-1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Neuronal ceroid lipofuscinosis 3 (3)
1	-	-	not provided (1)
1	-	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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: rs1555468634;

hg19: chr16-28497285;