NM_017882.3:c.*690A>G

Variant names:

• chr15-68207450-T-C
• rs8033190
• NM_017882.3:c.*690A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017882.3(CLN6):​c.*690A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 155,454 control chromosomes in the GnomAD database, including 971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (971 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (0 hom.)
• Consequence: CLN6 NM_017882.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.657
• Publications: 5 publications found

Genes affected

CLN6 (HGNC:2077): (CLN6 transmembrane ER protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function. [provided by RefSeq, Oct 2008]

CLN6 Gene-Disease associations (from GenCC):

• ceroid lipofuscinosis, neuronal, 6A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, Genomics England PanelApp, G2P
• ceroid lipofuscinosis, neuronal, 6B (Kufs type)

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp
• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000260007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 15-68207450-T-C is Benign according to our data. Variant chr15-68207450-T-C is described in ClinVar as Benign. ClinVar VariationId is 316972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017882.3. 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
	CLN6	NM_017882.3	MANE Select	c.*690A>G		3_prime_UTR	Exon 7 of 7	NP_060352.1	Q9NWW5-1
	CLN6	NM_001411068.1		c.*690A>G		3_prime_UTR	Exon 7 of 7	NP_001397997.1	Q9NWW5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN6	ENST00000249806.11	TSL:1 MANE Select	c.*690A>G		3_prime_UTR	Exon 7 of 7	ENSP00000249806.5	Q9NWW5-1
	ENSG00000260007	ENST00000562767.2	TSL:3	c.84-9822A>G		intron	N/A	ENSP00000456336.1	H3BRN7
	ENSG00000260007	ENST00000638026.1	TSL:1	n.231A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10323 AN: 152026 Hom.: 967 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0365

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00883

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.00755 AC: 25 AN: 3310 Hom.: 0 Cov.: 0 AF XY: 0.00833 AC XY: 15 AN XY: 1800

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AF: 0.0112 AC: 9 AN: 800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 38

South Asian (SAS) AF: 0.00680 AC: 2 AN: 294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00645 AC: 13 AN: 2014

Other (OTH) AF: 0.00926 AC: 1 AN: 108

GnomAD4 genome AF: 0.0680 AC: 10351 AN: 152144 Hom.: 971 Cov.: 33 AF XY: 0.0650 AC XY: 4832 AN XY: 74394

African (AFR) AF: 0.213 AC: 8841 AN: 41478

American (AMR) AF: 0.0326 AC: 498 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.0366 AC: 189 AN: 5166

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4830

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00881 AC: 599 AN: 67976

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0300 Hom.: 342

Bravo AF: 0.0778

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neuronal ceroid lipofuscinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8033190; hg19: chr15-68499788;