rs1387125116

Variant summary

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

The NM_001009566.3(CLSTN1):​c.2686G>T​(p.Gly896Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G896R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CLSTN1
NM_001009566.3 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
CLSTN1 (HGNC:17447): (calsyntenin 1) This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

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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 rank MANE Protein UniProt
CLSTN1NM_001009566.3 linkc.2686G>T p.Gly896Trp missense_variant Exon 18 of 19 ENST00000377298.9 NP_001009566.1 O94985-1
CLSTN1NM_014944.4 linkc.2656G>T p.Gly886Trp missense_variant Exon 17 of 18 NP_055759.3 O94985-2
CLSTN1NM_001302883.1 linkc.2629G>T p.Gly877Trp missense_variant Exon 17 of 18 NP_001289812.1 O94985B4E3Q1
CLSTN1XM_047449470.1 linkc.2599G>T p.Gly867Trp missense_variant Exon 16 of 17 XP_047305426.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLSTN1ENST00000377298.9 linkc.2686G>T p.Gly896Trp missense_variant Exon 18 of 19 1 NM_001009566.3 ENSP00000366513.4 O94985-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.062
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
2.0
M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-2.4
N;N;N
REVEL
Benign
0.28
Sift
Uncertain
0.0020
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.77
MutPred
0.13
Gain of MoRF binding (P = 0.0519);.;.;
MVP
0.54
MPC
1.0
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.31
gMVP
0.33

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

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

Other links and lift over

dbSNP: rs1387125116; hg19: chr1-9791326; API