chr3-140532659-A-G

Variant names:

• chr3-140532659-A-G
• rs10513119
• NM_022131.3:c.1507+173A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022131.3(CLSTN2):​c.1507+173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 152,320 control chromosomes in the GnomAD database, including 419 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 0.057 (419 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.1507+173A>G		intron_variant	Intron 9 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.1432+173A>G		intron_variant	Intron 9 of 16		XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.1507+173A>G		intron_variant	Intron 9 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.1695+173A>G		intron_variant	Intron 9 of 10	2

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8656 AN: 152202 Hom.: 416 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0570 AC: 8685 AN: 152320 Hom.: 419 Cov.: 32 AF XY: 0.0586 AC XY: 4366 AN XY: 74476

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0370 Hom.: 55

Bravo AF: 0.0642

Asia WGS AF: 0.118 AC: 408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.27

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

Other links and lift over

dbSNP: rs10513119; hg19: chr3-140251501;