rs308952

Variant names:

• chr3-12154122-A-G
• rs308952
• NM_133625.6:c.774+2796A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-12154122-A-G
• chr3-12154122-A-T

Variant summary

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

The NM_133625.6(SYN2):​c.774+2796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,192 control chromosomes in the GnomAD database, including 51,823 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 0.82 (51823 hom., cov: 33)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 7 publications found

Genes affected

SYN2 (HGNC:11495): (synapsin II) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Polymorphisms in this gene are associated with abnormal presynaptic function and related neuronal disorders, including autism, epilepsy, bipolar disorder and schizophrenia. Alternative splicing of this gene results in multiple transcript variants. The tissue inhibitor of metalloproteinase 4 gene is located within an intron of this gene and is transcribed in the opposite direction. [provided by RefSeq, Feb 2014]

TIMP4 (HGNC:11823): (TIMP metallopeptidase inhibitor 4) This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.774+2796A>G		intron_variant	Intron 5 of 12	ENST00000621198.5	NP_598328.1
TIMP4	NM_003256.4	c.477+205T>C		intron_variant	Intron 4 of 4	ENST00000287814.5	NP_003247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.774+2796A>G		intron_variant	Intron 5 of 12	1	NM_133625.6	ENSP00000480050.1
TIMP4	ENST00000287814.5	c.477+205T>C		intron_variant	Intron 4 of 4	1	NM_003256.4	ENSP00000287814.4
SYN2	ENST00000620175.4	c.774+2796A>G		intron_variant	Intron 5 of 10	1		ENSP00000484916.1
SYN2	ENST00000439861.5	n.225+2796A>G		intron_variant	Intron 2 of 9	2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124729 AN: 152074 Hom.: 51784 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.820 AC: 124816 AN: 152192 Hom.: 51823 Cov.: 33 AF XY: 0.825 AC XY: 61427 AN XY: 74420

African (AFR) AF: 0.672 AC: 27902 AN: 41496

American (AMR) AF: 0.890 AC: 13609 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3157 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4188 AN: 5176

South Asian (SAS) AF: 0.906 AC: 4375 AN: 4828

European-Finnish (FIN) AF: 0.911 AC: 9663 AN: 10612

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59026 AN: 68000

Other (OTH) AF: 0.846 AC: 1787 AN: 2112

Alfa AF: 0.850 Hom.: 30917

Bravo AF: 0.811

Asia WGS AF: 0.878 AC: 3051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-0.37
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: rs308952; hg19: chr3-12195622;