rs598747

Variant names:

• chr3-12070510-G-A
• rs598747
• NM_133625.6:c.377+65582G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACTG1P12 (HGNC:44496): (actin gamma 1 pseudogene 12)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.377+65582G>A		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.377+65582G>A		intron	N/A	NP_003169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.377+65582G>A		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.377+65582G>A		intron	N/A	ENSP00000484916.1
	ACTG1P12	ENST00000423183.1	TSL:6	n.316G>A		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.696 AC: 10280 AN: 14780

American (AMR) AF: 0.939 AC: 36312 AN: 38674

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 13605 AN: 14818

East Asian (EAS) AF: 0.799 AC: 14818 AN: 18542

South Asian (SAS) AF: 0.929 AC: 65122 AN: 70062

European-Finnish (FIN) AF: 0.896 AC: 33707 AN: 37628

Middle Eastern (MID) AF: 0.930 AC: 2815 AN: 3028

European-Non Finnish (NFE) AF: 0.862 AC: 314616 AN: 364994

Other (OTH) AF: 0.871 AC: 22668 AN: 26024

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

African (AFR) AF: 0.694 AC: 28789 AN: 41484

American (AMR) AF: 0.891 AC: 13641 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3171 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4155 AN: 5144

South Asian (SAS) AF: 0.916 AC: 4411 AN: 4816

European-Finnish (FIN) AF: 0.902 AC: 9566 AN: 10608

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58385 AN: 67992

Other (OTH) AF: 0.847 AC: 1785 AN: 2108

Alfa AF: 0.840 Hom.: 9404

Bravo AF: 0.814

Asia WGS AF: 0.882 AC: 3065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		3.8

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: rs598747; hg19: chr3-12112010;