Variant chr3-12070553-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000621198.5(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
ENST00000621198.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.846

Variant links:

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]

SYN2 links:

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

ACTG1P12 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE	Protein
SYN2	NM_133625.6 linkuse as main transcript	c.377+65625G>A	intron_variant	ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6 linkuse as main transcript	c.377+65625G>A	intron_variant		NP_003169.2
SYN2	XM_006713311.4 linkuse as main transcript	c.377+65625G>A	intron_variant		XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5 linkuse as main transcript	c.377+65625G>A	intron_variant		1	NM_133625.6	ENSP00000480050	P2	Q92777-1
SYN2	ENST00000620175.4 linkuse as main transcript	c.377+65625G>A	intron_variant		1		ENSP00000484916	A2	Q92777-2
ACTG1P12	ENST00000423183.1 linkuse as main transcript	n.359G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96463

AN:

151936

Hom.:

33204

Cov.:

show subpopulations

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.:

AF XY:

0.747

AC XY:

365475

AN XY:

489082

show subpopulations

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.:

AF XY:

0.641

AC XY:

47620

AN XY:

74322

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over