Genetic Variant NM_133625.6:c.378-32137G>T (chr3-12108514-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133625.6(SYN2):c.378-32137G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,122 control chromosomes in the GnomAD database, including 9,252 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 0.33 ( 9252 hom., cov: 32)

Consequence

SYN2
NM_133625.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

8 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 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.378-32137G>T		intron	N/A	NP_598328.1	Q92777-1
	SYN2	NM_003178.6		c.378-32137G>T		intron	N/A	NP_003169.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYN2	ENST00000621198.5	TSL:1 MANE Select	c.378-32137G>T	intron	N/A	ENSP00000480050.1	Q92777-1
SYN2	ENST00000620175.4	TSL:1	c.378-32137G>T	intron	N/A	ENSP00000484916.1	Q92777-2
SYN2	ENST00000424884.1	TSL:4	n.127-32137G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50071

AN:

152004

Hom.:

9248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.0865

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.329

AC:

50092

AN:

152122

Hom.:

9252

Cov.:

AF XY:

0.323

AC XY:

24029

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.186

AC:

7719

AN:

41518

American (AMR)

AF:

0.400

AC:

6114

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1465

AN:

3468

East Asian (EAS)

AF:

0.0871

AC:

451

AN:

5176

South Asian (SAS)

AF:

0.233

AC:

1124

AN:

4828

European-Finnish (FIN)

AF:

0.348

AC:

3677

AN:

10564

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.414

AC:

28171

AN:

67974

Other (OTH)

AF:

0.372

AC:

786

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1642

3283

4925

6566

8208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.393

Hom.:

20581

Bravo

AF:

0.331

Asia WGS

AF:

0.178

AC:

620

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

(source)

DANN

Benign

0.41

PhyloP100

-0.15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over