rs598704

Variant names:

• chr3-12070553-G-A
• rs598704
• NM_133625.6:c.377+65625G>A

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+65625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,107,620 control chromosomes in the GnomAD database, including 300,559 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 0.63 (33220 hom., cov: 32)
  • Exomes 𝑓: 0.74 (267339 hom.)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 2 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.377+65625G>A		intron_variant	Intron 1 of 12	ENST00000621198.5	NP_598328.1
ACTG1P12		n.12070553G>A		intragenic_variant
SYN2	NM_003178.6	c.377+65625G>A		intron_variant	Intron 1 of 10		NP_003169.2
SYN2	XM_006713311.4	c.377+65625G>A		intron_variant	Intron 1 of 10		XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.377+65625G>A		intron_variant	Intron 1 of 12	1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.377+65625G>A		intron_variant	Intron 1 of 10	1		ENSP00000484916.1
ACTG1P12	ENST00000423183.1	n.359G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96463 AN: 151936 Hom.: 33204 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.744 AC: 711119 AN: 955566 Hom.: 267339 Cov.: 13 AF XY: 0.747 AC XY: 365475 AN XY: 489082

African (AFR) AF: 0.333 AC: 7241 AN: 21772

American (AMR) AF: 0.852 AC: 33692 AN: 39556

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 13007 AN: 17468

East Asian (EAS) AF: 0.627 AC: 13027 AN: 20774

South Asian (SAS) AF: 0.807 AC: 61906 AN: 76720

European-Finnish (FIN) AF: 0.773 AC: 30940 AN: 40040

Middle Eastern (MID) AF: 0.793 AC: 3199 AN: 4036

European-Non Finnish (NFE) AF: 0.746 AC: 519718 AN: 696556

Other (OTH) AF: 0.735 AC: 28389 AN: 38644

GnomAD4 genome AF: 0.635 AC: 96497 AN: 152054 Hom.: 33220 Cov.: 32 AF XY: 0.641 AC XY: 47620 AN XY: 74322

African (AFR) AF: 0.342 AC: 14172 AN: 41460

American (AMR) AF: 0.755 AC: 11547 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2532 AN: 3468

East Asian (EAS) AF: 0.634 AC: 3260 AN: 5138

South Asian (SAS) AF: 0.784 AC: 3780 AN: 4822

European-Finnish (FIN) AF: 0.782 AC: 8275 AN: 10582

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50425 AN: 67986

Other (OTH) AF: 0.695 AC: 1465 AN: 2108

Alfa AF: 0.682 Hom.: 10839

Bravo AF: 0.619

Asia WGS AF: 0.696 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.73
DANN	Benign	0.57
PhyloP100		-0.85

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: rs598704; hg19: chr3-12112053; COSMIC: COSV70285845; COSMIC: COSV70285845;