Genetic Variant NM_022131.3:c.67G>A (chr3-139935441-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022131.3(CLSTN2):c.67G>A(p.Gly23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000731 in 1,231,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CLSTN2
NM_022131.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.582

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08159369).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022131.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSTN2	NM_022131.3	MANE Select	c.67G>A	p.Gly23Ser	missense	Exon 1 of 17	NP_071414.2	Q9H4D0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSTN2	ENST00000458420.7	TSL:1 MANE Select	c.67G>A	p.Gly23Ser	missense	Exon 1 of 17	ENSP00000402460.2	Q9H4D0
	CLSTN2	ENST00000511524.1	TSL:2	n.255G>A		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000648

AC:

AN:

1079562

Hom.:

Cov.:

AF XY:

0.00000785

AC XY:

AN XY:

509766

show subpopulations

African (AFR)

AF:

0.0000436

AC:

AN:

22932

American (AMR)

AF:

0.00

AC:

AN:

8384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14336

East Asian (EAS)

AF:

0.000226

AC:

AN:

26496

South Asian (SAS)

AF:

0.00

AC:

AN:

19490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919574

Other (OTH)

AF:

0.00

AC:

AN:

43658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000391

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.084

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-0.58

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.25

REVEL

Benign

0.058

Sift

Benign

0.17

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.12

MutPred

0.29

Gain of glycosylation at G23 (P = 0.0037)

MVP

0.30

MPC

0.62

ClinPred

0.48

GERP RS

-1.1

PromoterAI

-0.0044

Neutral

(source)

Varity_R

0.064

gMVP

0.24

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over