3-12167171-G-T

Position:

• chr3-12167171-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.981-63G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,542,288 control chromosomes in the GnomAD database, including 434,988 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 0.72 (40086 hom., cov: 32)
  • Exomes 𝑓: 0.75 (394902 hom.)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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]

SYN2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.981-63G>T		intron_variant		ENST00000621198.5	NP_598328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.981-63G>T		intron_variant		1	NM_133625.6	ENSP00000480050.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109894 AN: 152026 Hom.: 40054 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.753 AC: 1046301 AN: 1390144 Hom.: 394902 AF XY: 0.754 AC XY: 519772 AN XY: 689804

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.740

Gnomad4 EAS exome AF: 0.665

Gnomad4 SAS exome AF: 0.805

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.751

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.723 AC: 109971 AN: 152144 Hom.: 40086 Cov.: 32 AF XY: 0.727 AC XY: 54063 AN XY: 74382

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.759

Alfa AF: 0.721 Hom.: 9440

Bravo AF: 0.719

Asia WGS AF: 0.735 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.73

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: rs795009; hg19: chr3-12208671;