rs143728911

Positions:

• chr15-68208244-C-G
• chr15-68208244-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017882.3(CLN6):​c.832G>C​(p.Ala278Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLN6 NM_017882.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN6	NM_017882.3	c.832G>C	p.Ala278Pro	missense_variant	7/7	ENST00000249806.11	NP_060352.1
CLN6	NM_001411068.1	c.928G>C	p.Ala310Pro	missense_variant	7/7		NP_001397997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN6	ENST00000249806.11	c.832G>C	p.Ala278Pro	missense_variant	7/7	1	NM_017882.3	ENSP00000249806	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D;D;D;.;T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.092
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	1.4	L;.;.;.;.;.
MutationTaster	Benign	0.62	D;D;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N;D;N;N;.;.
REVEL	Pathogenic	0.67
Sift	Benign	0.14	T;T;T;T;.;.
Sift4G	Benign	0.086	T;D;D;T;.;.
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.50
MutPred		0.46		.;.;.;Loss of catalytic residue at A310 (P = 0.0247);.;.;
MVP		0.94
MPC		0.64
ClinPred		0.87	D
GERP RS		3.3
Varity_R		0.47
gMVP		0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs143728911; hg19: chr15-68500582;