rs308971

chr3-12075120-G-Achr3-12075120-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN2	NM_133625.6	c.378-65531G>A		intron_variant		ENST00000621198.5
SYN2	NM_003178.6	c.378-65531G>A		intron_variant
SYN2	XM_006713311.4	c.378-65531G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN2	ENST00000621198.5	c.378-65531G>A		intron_variant		1	NM_133625.6	P2
SYN2	ENST00000620175.4	c.378-65531G>A		intron_variant		1		A2
SYN2	ENST00000424884.1	n.126+3437G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.848

Alfa AF: 0.860 Hom.: 41285

Bravo AF: 0.817

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.28
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: rs308971; hg19: chr3-12116620;