Variant 1-9730601-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001009566.3(CLSTN1):c.2853G>C(p.Glu951Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,610,268 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E951G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 65 hom. )

Consequence

CLSTN1
NM_001009566.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.953

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]

CLSTN1 links:

CLSTN1 (HGNC:):

CLSTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058742464).

BP6

Variant 1-9730601-C-G is Benign according to our data. Variant chr1-9730601-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638191.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 811 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSTN1	NM_001009566.3 linkuse as main transcript	c.2853G>C	p.Glu951Asp	missense_variant	19/19	ENST00000377298.9	NP_001009566.1	O94985-1
CLSTN1	NM_014944.4 linkuse as main transcript	c.2823G>C	p.Glu941Asp	missense_variant	18/18		NP_055759.3	O94985-2
CLSTN1	NM_001302883.1 linkuse as main transcript	c.2796G>C	p.Glu932Asp	missense_variant	18/18		NP_001289812.1	O94985B4E3Q1
CLSTN1	XM_047449470.1 linkuse as main transcript	c.2766G>C	p.Glu922Asp	missense_variant	17/17		XP_047305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSTN1	ENST00000377298.9 linkuse as main transcript	c.2853G>C	p.Glu951Asp	missense_variant	19/19	1	NM_001009566.3	ENSP00000366513.4		O94985-1

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

811

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00538

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00837

Gnomad OTH

AF:

0.00914

GnomAD3 exomes

AF:

0.00501

AC:

1248

AN:

248872

Hom.:

AF XY:

0.00513

AC XY:

691

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00647

Gnomad NFE exome

AF:

0.00782

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00824

AC:

12016

AN:

1458154

Hom.:

Cov.:

AF XY:

0.00805

AC XY:

5845

AN XY:

725648

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00670

Gnomad4 NFE exome

AF:

0.00983

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.00533

AC:

811

AN:

152114

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

373

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00613

Gnomad4 NFE

AF:

0.00837

Gnomad4 OTH

AF:

0.00905

Alfa

AF:

0.00746

Hom.:

Bravo

AF:

0.00540

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00480

AC:

583

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

CLSTN1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.15

N;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.90

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.016

B;.;B

Vest4

0.19

MutPred

0.065

Gain of loop (P = 0.1069);.;.;

MVP

0.36

MPC

0.27

ClinPred

0.0084

GERP RS

2.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.030

gMVP

0.019

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over