rs553192210

Variant names:

• chr15-68214177-C-A
• rs553192210
• NM_017882.3:c.297+113G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-68214177-C-A
• chr15-68214177-C-G

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.297+113G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000359 in 835,110 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CLN6 NM_017882.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 1 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
• ceroid lipofuscinosis, neuronal, 6B (Kufs type)

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
• 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=-0.75).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN6	NM_017882.3	MANE Select	c.297+113G>T		intron	N/A	NP_060352.1
	CLN6	NM_001411068.1		c.393+113G>T		intron	N/A	NP_001397997.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN6	ENST00000249806.11	TSL:1 MANE Select	c.297+113G>T		intron	N/A	ENSP00000249806.5
	CLN6	ENST00000637667.1	TSL:1	c.199-2314G>T		intron	N/A	ENSP00000489843.1
	CLN6	ENST00000566347.5	TSL:1	c.297+113G>T		intron	N/A	ENSP00000457783.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000293 AC: 2 AN: 682726 Hom.: 0 Cov.: 9 AF XY: 0.00000278 AC XY: 1 AN XY: 359816

African (AFR) AF: 0.00 AC: 0 AN: 17932

American (AMR) AF: 0.00 AC: 0 AN: 35960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19288

East Asian (EAS) AF: 0.00 AC: 0 AN: 32694

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 63928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4198

European-Non Finnish (NFE) AF: 0.00000234 AC: 1 AN: 426722

Other (OTH) AF: 0.00 AC: 0 AN: 34038

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152384 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74526

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.81
PhyloP100		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: rs553192210; hg19: chr15-68506515;