rs747144655

Variant names:

• chr15-68207828-G-A
• rs747144655
• NM_017882.3:c.*312C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-68207828-G-A
• chr15-68207828-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017882.3(CLN6):​c.*312C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 431,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: CLN6 NM_017882.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.783
• 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: Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
• ceroid lipofuscinosis, neuronal, 6B (Kufs type)

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

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000260007 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.*312C>T		3_prime_UTR	Exon 7 of 7	NP_060352.1	Q9NWW5-1
	CLN6	NM_001411068.1		c.*312C>T		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.*312C>T		3_prime_UTR	Exon 7 of 7	ENSP00000249806.5	Q9NWW5-1
	ENSG00000260007	ENST00000562767.2	TSL:3	c.84-10200C>T		intron	N/A	ENSP00000456336.1	H3BRN7
	CLN6	ENST00000638076.1	TSL:1	n.*851C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000490373.1	A0A0S2Z5D0

Frequencies

GnomAD3 genomes AF: 0.000592 AC: 90 AN: 152130 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.000958

GnomAD4 exome AF: 0.000626 AC: 175 AN: 279398 Hom.: 0 Cov.: 0 AF XY: 0.000603 AC XY: 90 AN XY: 149366

African (AFR) AF: 0.00 AC: 0 AN: 8258

American (AMR) AF: 0.000616 AC: 8 AN: 12996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8052

East Asian (EAS) AF: 0.00 AC: 0 AN: 15498

South Asian (SAS) AF: 0.0000236 AC: 1 AN: 42324

European-Finnish (FIN) AF: 0.000228 AC: 3 AN: 13148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1122

European-Non Finnish (NFE) AF: 0.000921 AC: 150 AN: 162876

Other (OTH) AF: 0.000860 AC: 13 AN: 15124

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152248 Hom.: 1 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74452

African (AFR) AF: 0.000193 AC: 8 AN: 41540

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68000

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.88
CADD	Benign	0.36
DANN	Benign	0.54
PhyloP100		-0.78

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: rs747144655; hg19: chr15-68500166;