3-140403798-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022131.3(CLSTN2):​c.402C>G​(p.His134Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H134H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

CLSTN2
NM_022131.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038333744).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLSTN2NM_022131.3 linkc.402C>G p.His134Gln missense_variant Exon 3 of 17 ENST00000458420.7 NP_071414.2 Q9H4D0
CLSTN2XM_017007022.3 linkc.327C>G p.His109Gln missense_variant Exon 3 of 17 XP_016862511.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLSTN2ENST00000458420.7 linkc.402C>G p.His134Gln missense_variant Exon 3 of 17 1 NM_022131.3 ENSP00000402460.2 Q9H4D0
CLSTN2ENST00000511524.1 linkn.590C>G non_coding_transcript_exon_variant Exon 3 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249282
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134624
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1459918
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000327
Hom.:
0
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
3.0
DANN
Benign
0.89
DEOGEN2
Benign
0.075
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.59
N
REVEL
Benign
0.014
Sift
Benign
0.10
T
Sift4G
Benign
0.13
T
Polyphen
0.0010
B
Vest4
0.17
MutPred
0.30
Loss of disorder (P = 0.1437);
MVP
0.23
MPC
0.18
ClinPred
0.025
T
GERP RS
-2.8
Varity_R
0.080
gMVP
0.093

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: rs368696603; hg19: chr3-140122640; API