NM_022131.3:c.109+34090G>A

Variant names:

• chr3-139969573-G-A
• rs6806737
• NM_022131.3:c.109+34090G>A

Variant summary

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

The NM_022131.3(CLSTN2):​c.109+34090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,082 control chromosomes in the GnomAD database, including 1,497 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 0.13 (1497 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+34090G>A		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.109+34090G>A		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.297+34090G>A		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20492 AN: 151964 Hom.: 1495 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.135 AC: 20504 AN: 152082 Hom.: 1497 Cov.: 32 AF XY: 0.132 AC XY: 9839 AN XY: 74340

African (AFR) AF: 0.165 AC: 6856 AN: 41464

American (AMR) AF: 0.0850 AC: 1299 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3468

East Asian (EAS) AF: 0.0860 AC: 446 AN: 5186

South Asian (SAS) AF: 0.0880 AC: 423 AN: 4806

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10588

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9091 AN: 67976

Other (OTH) AF: 0.115 AC: 242 AN: 2104

Alfa AF: 0.128 Hom.: 2236

Bravo AF: 0.131

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.037
DANN	Benign	0.37
PhyloP100		-1.6
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: rs6806737; hg19: chr3-139688415;