rs598704

chr3-12070553-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SYN2	NM_133625.6	c.377+65625G>A		intron_variant		ENST00000621198.5
SYN2	NM_003178.6	c.377+65625G>A		intron_variant
SYN2	XM_006713311.4	c.377+65625G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN2	ENST00000621198.5	c.377+65625G>A		intron_variant		1	NM_133625.6	P2
SYN2	ENST00000620175.4	c.377+65625G>A		intron_variant		1		A2
ACTG1P12	ENST00000423183.1	n.359G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.852

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.807

Gnomad4 FIN exome AF: 0.773

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.735

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

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.695

Alfa AF: 0.698 Hom.: 9950

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

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