3-140065285-C-T

Variant names:

• chr3-140065285-C-T
• rs12496538
• NM_022131.3:c.110-110666C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022131.3(CLSTN2):​c.110-110666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,060 control chromosomes in the GnomAD database, including 13,532 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13532 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.110-110666C>T		intron_variant	Intron 1 of 16	ENST00000458420.7	NP_071414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.110-110666C>T		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.298-110666C>T		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59605 AN: 151942 Hom.: 13486 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59708 AN: 152060 Hom.: 13532 Cov.: 32 AF XY: 0.392 AC XY: 29126 AN XY: 74334

African (AFR) AF: 0.601 AC: 24936 AN: 41494

American (AMR) AF: 0.462 AC: 7064 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2868 AN: 5146

South Asian (SAS) AF: 0.198 AC: 955 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2649 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19285 AN: 67958

Other (OTH) AF: 0.378 AC: 797 AN: 2110

Alfa AF: 0.346 Hom.: 6989

Bravo AF: 0.425

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.74
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12496538; hg19: chr3-139784127;