rs377192977

Variant summary

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

The NM_017882.3(CLN6):​c.733G>T​(p.Val245Phe) 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

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12
Variant links:
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 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
CLN6NM_017882.3 linkc.733G>T p.Val245Phe missense_variant 7/7 ENST00000249806.11 NP_060352.1 Q9NWW5-1A0A024R601
CLN6NM_001411068.1 linkc.829G>T p.Val277Phe missense_variant 7/7 NP_001397997.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLN6ENST00000249806.11 linkc.733G>T p.Val245Phe missense_variant 7/71 NM_017882.3 ENSP00000249806.5 Q9NWW5-1
ENSG00000260007ENST00000562767.2 linkc.84-10715G>T intron_variant 3 ENSP00000456336.1 H3BRN7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.23
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.92
D;D;D;.;T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Uncertain
0.74
D;D;D;D;D;D
MetaSVM
Pathogenic
0.86
D
MutationAssessor
Benign
1.7
L;.;.;.;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.0
D;D;D;D;.;.
REVEL
Pathogenic
0.76
Sift
Benign
0.071
T;T;T;T;.;.
Sift4G
Benign
0.075
T;T;T;T;.;.
Polyphen
0.18
B;.;.;.;.;.
Vest4
0.74
MVP
0.96
MPC
0.99
ClinPred
0.97
D
GERP RS
5.2
Varity_R
0.17
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377192977; hg19: chr15-68500681; API