3-12075120-G-A

Variant names:

• chr3-12075120-G-A
• rs308971
• NM_133625.6:c.378-65531G>A

Variant summary

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

The NM_133625.6(SYN2):​c.378-65531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,032 control chromosomes in the GnomAD database, including 52,199 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 (52199 hom., cov: 31)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 25 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133625.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.378-65531G>A		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.378-65531G>A		intron	N/A	NP_003169.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.378-65531G>A		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.378-65531G>A		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000424884.1	TSL:4	n.126+3437G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125295 AN: 151914 Hom.: 52159 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.825 AC: 125388 AN: 152032 Hom.: 52199 Cov.: 31 AF XY: 0.830 AC XY: 61706 AN XY: 74338

African (AFR) AF: 0.693 AC: 28698 AN: 41428

American (AMR) AF: 0.892 AC: 13604 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3170 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4193 AN: 5184

South Asian (SAS) AF: 0.915 AC: 4418 AN: 4826

European-Finnish (FIN) AF: 0.908 AC: 9613 AN: 10582

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

European-Non Finnish (NFE) AF: 0.865 AC: 58792 AN: 67974

Other (OTH) AF: 0.848 AC: 1791 AN: 2112

Alfa AF: 0.852 Hom.: 156858

Bravo AF: 0.817

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.27
PhyloP100		-0.47

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: rs308971; hg19: chr3-12116620;