rs886051437

Variant names:

• chr15-68207608-A-G
• rs886051437
• NM_017882.3:c.*532T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-68207608-A-G
• chr15-68207608-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017882.3(CLN6):​c.*532T>C variant causes a 3 prime UTR 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLN6 NM_017882.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.*532T>C		3_prime_UTR	Exon 7 of 7	NP_060352.1	Q9NWW5-1
	CLN6	NM_001411068.1		c.*532T>C		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.*532T>C		3_prime_UTR	Exon 7 of 7	ENSP00000249806.5	Q9NWW5-1
	ENSG00000260007	ENST00000562767.2	TSL:3	c.84-9980T>C		intron	N/A	ENSP00000456336.1	H3BRN7
	ENSG00000260007	ENST00000638026.1	TSL:1	n.73T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 45274 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 23772

African (AFR) AF: 0.00 AC: 0 AN: 1610

American (AMR) AF: 0.00 AC: 0 AN: 3624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 944

East Asian (EAS) AF: 0.00 AC: 0 AN: 2994

South Asian (SAS) AF: 0.00 AC: 0 AN: 5934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26720

Other (OTH) AF: 0.00 AC: 0 AN: 2118

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.64
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs886051437; hg19: chr15-68499946;