3-140542845-A-T

Variant names:

• chr3-140542845-A-T
• rs349558
• NM_022131.3:c.1508-3670A>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.1508-3670A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,118 control chromosomes in the GnomAD database, including 2,486 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 0.18 (2486 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 2 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]

CLSTN2-AS1 (HGNC:49095): (CLSTN2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.1508-3670A>T		intron_variant	Intron 9 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.1433-3670A>T		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.1508-3670A>T		intron_variant	Intron 9 of 16	1	NM_022131.3	ENSP00000402460.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27081 AN: 152000 Hom.: 2483 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.178 AC: 27095 AN: 152118 Hom.: 2486 Cov.: 32 AF XY: 0.171 AC XY: 12698 AN XY: 74378

African (AFR) AF: 0.167 AC: 6948 AN: 41504

American (AMR) AF: 0.173 AC: 2639 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3472

East Asian (EAS) AF: 0.161 AC: 829 AN: 5160

South Asian (SAS) AF: 0.0896 AC: 432 AN: 4822

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13961 AN: 67972

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.178 Hom.: 301

Bravo AF: 0.183

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.49
PhyloP100		-0.14
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: rs349558; hg19: chr3-140261687;