rs753538013
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_017882.3(CLN6):c.522G>A(p.Glu174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CLN6
NM_017882.3 synonymous
NM_017882.3 synonymous
Scores
1
1
9
Clinical Significance
Conservation
PhyloP100: 0.170
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20365572).
BP6
?
Variant 15-68211283-C-T is Benign according to our data. Variant chr15-68211283-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 527772.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.17 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLN6 | NM_017882.3 | c.522G>A | p.Glu174= | synonymous_variant | 5/7 | ENST00000249806.11 | |
CLN6 | NM_001411068.1 | c.618G>A | p.Glu206= | synonymous_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLN6 | ENST00000249806.11 | c.522G>A | p.Glu174= | synonymous_variant | 5/7 | 1 | NM_017882.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251060Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727174
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GnomAD4 genome ? Cov.: 32
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32
ExAC
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuronal ceroid lipofuscinosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MutationTaster
Benign
D;D;D;D;D;N
PROVEAN
Benign
N;.
Sift
Benign
T;.
Sift4G
Benign
T;.
Vest4
MVP
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at