Variant rs17348572 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022131.3(CLSTN2):c.992T>C(p.Ile331Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,613,962 control chromosomes in the GnomAD database, including 2,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.040 ( 146 hom., cov: 32)

Exomes 𝑓: 0.050 ( 1961 hom. )

Consequence

CLSTN2
NM_022131.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

CLSTN2 (HGNC:17448): (calsyntenin 2) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of synapse assembly and positive regulation of synaptic transmission. Predicted to be located in postsynaptic density. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLSTN2 links:

CLSTN2 (HGNC:):

CLSTN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021517873).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSTN2	NM_022131.3 linkuse as main transcript	c.992T>C	p.Ile331Thr	missense_variant	7/17	ENST00000458420.7	NP_071414.2	Q9H4D0
CLSTN2	XM_017007022.3 linkuse as main transcript	c.917T>C	p.Ile306Thr	missense_variant	7/17		XP_016862511.1
LOC105374132	XR_007096117.1 linkuse as main transcript	n.49-4786A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLSTN2	ENST00000458420.7 linkuse as main transcript	c.992T>C	p.Ile331Thr	missense_variant	7/17	1	NM_022131.3	ENSP00000402460.2	Q9H4D0
CLSTN2	ENST00000511524.1 linkuse as main transcript	n.1180T>C		non_coding_transcript_exon_variant	7/11	2
ENSG00000249290	ENST00000503357.1 linkuse as main transcript	n.100+713A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6063

AN:

152132

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0538

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0414

AC:

10382

AN:

250710

Hom.:

236

AF XY:

0.0425

AC XY:

5761

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.0216

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0324

Gnomad EAS exome

AF:

0.0252

Gnomad SAS exome

AF:

0.0360

Gnomad FIN exome

AF:

0.0546

Gnomad NFE exome

AF:

0.0532

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0504

AC:

73739

AN:

1461712

Hom.:

1961

Cov.:

AF XY:

0.0503

AC XY:

36547

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0359

Gnomad4 EAS exome

AF:

0.0270

Gnomad4 SAS exome

AF:

0.0367

Gnomad4 FIN exome

AF:

0.0562

Gnomad4 NFE exome

AF:

0.0550

Gnomad4 OTH exome

AF:

0.0441

GnomAD4 genome

AF:

0.0398

AC:

6064

AN:

152250

Hom.:

146

Cov.:

AF XY:

0.0399

AC XY:

2972

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.0267

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0545

Gnomad4 NFE

AF:

0.0538

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0489

Hom.:

503

Bravo

AF:

0.0367

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0597

AC:

230

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.0524

AC:

451

ExAC

AF:

0.0416

AC:

5054

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.0499

EpiControl

AF:

0.0510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.22

Eigen

Benign

-0.18

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

REVEL

Benign

0.045

Sift

Benign

0.23

Sift4G

Benign

0.49

Polyphen

0.010

Vest4

0.12

MPC

0.23

ClinPred

0.0093

GERP RS

5.4

Varity_R

0.20

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over