3-12167171-G-T

Variant names:

• chr3-12167171-G-T
• rs795009
• NM_133625.6:c.981-63G>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.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
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 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.981-63G>T		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.981-63G>T		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.981-63G>T		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.981-63G>T		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000425297.2	TSL:5	n.207-63G>T		intron	N/A	ENSP00000480038.1

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

African (AFR) AF: 0.620 AC: 19847 AN: 32002

American (AMR) AF: 0.860 AC: 32967 AN: 38322

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 18617 AN: 25168

East Asian (EAS) AF: 0.665 AC: 25146 AN: 37806

South Asian (SAS) AF: 0.805 AC: 64702 AN: 80376

European-Finnish (FIN) AF: 0.777 AC: 39609 AN: 50970

Middle Eastern (MID) AF: 0.811 AC: 4585 AN: 5652

European-Non Finnish (NFE) AF: 0.751 AC: 797135 AN: 1061918

Other (OTH) AF: 0.754 AC: 43693 AN: 57930

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

African (AFR) AF: 0.628 AC: 26026 AN: 41468

American (AMR) AF: 0.794 AC: 12152 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2533 AN: 3470

East Asian (EAS) AF: 0.681 AC: 3524 AN: 5176

South Asian (SAS) AF: 0.789 AC: 3794 AN: 4806

European-Finnish (FIN) AF: 0.788 AC: 8349 AN: 10600

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50933 AN: 68012

Other (OTH) AF: 0.759 AC: 1601 AN: 2110

Alfa AF: 0.718 Hom.: 10754

Bravo AF: 0.719

Asia WGS AF: 0.735 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		-0.43

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: rs795009; hg19: chr3-12208671;