rs598747

Positions:

• chr3-12070510-G-A
• chr3-12070510-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133625.6(SYN2):​c.377+65582G>A variant causes a intron change. The variant allele was found at a frequency of 0.863 in 740,684 control chromosomes in the GnomAD database, including 276,790 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 (51810 hom., cov: 31)
  • Exomes 𝑓: 0.87 (224980 hom.)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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]

ACTG1P12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• 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	Protein	UniProt
SYN2	NM_133625.6	c.377+65582G>A		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6	c.377+65582G>A		intron_variant			NP_003169.2
SYN2	XM_006713311.4	c.377+65582G>A		intron_variant			XP_006713374.1
ACTG1P12		n.12070510G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.377+65582G>A		intron_variant		1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.377+65582G>A		intron_variant		1		ENSP00000484916.1
ACTG1P12	ENST00000423183.1	n.316G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124903 AN: 152016 Hom.: 51769 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.873 AC: 513943 AN: 588550 Hom.: 224980 Cov.: 7 AF XY: 0.877 AC XY: 278781 AN XY: 317772

Gnomad4 AFR exome AF: 0.696

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.862

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.822 AC: 124997 AN: 152134 Hom.: 51810 Cov.: 31 AF XY: 0.827 AC XY: 61518 AN XY: 74360

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.847

Alfa AF: 0.844 Hom.: 9204

Bravo AF: 0.814

Asia WGS AF: 0.882 AC: 3065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.59

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: rs598747; hg19: chr3-12112010;