rs1387125116

Variant names:

• chr1-9731268-C-A
• rs1387125116
• NM_001009566.3:c.2686G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-9731268-C-A
• chr1-9731268-C-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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]

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 rank	MANE	Protein	UniProt
CLSTN1	NM_001009566.3	c.2686G>T	p.Gly896Trp	missense_variant	Exon 18 of 19	ENST00000377298.9	NP_001009566.1
CLSTN1	NM_014944.4	c.2656G>T	p.Gly886Trp	missense_variant	Exon 17 of 18		NP_055759.3
CLSTN1	NM_001302883.1	c.2629G>T	p.Gly877Trp	missense_variant	Exon 17 of 18		NP_001289812.1
CLSTN1	XM_047449470.1	c.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
CLSTN1	ENST00000377298.9	c.2686G>T	p.Gly896Trp	missense_variant	Exon 18 of 19	1	NM_001009566.3	ENSP00000366513.4

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

Other links and lift over

dbSNP: rs1387125116; hg19: chr1-9791326;