chr3-12156497-C-T

Variant names:

• chr3-12156497-C-T
• rs308953
• NM_133625.6:c.775-5049C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133625.6(SYN2):​c.775-5049C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,298 control chromosomes in the GnomAD database, including 66,797 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 0.94 (66797 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 5 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]

TIMP4 (HGNC:11823): (TIMP metallopeptidase inhibitor 4) This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.775-5049C>T		intron	N/A	NP_598328.1
	TIMP4	NM_003256.4	MANE Select	c.352+323G>A		intron	N/A	NP_003247.1
	SYN2	NM_003178.6		c.775-5049C>T		intron	N/A	NP_003169.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.775-5049C>T		intron	N/A	ENSP00000480050.1
	TIMP4	ENST00000287814.5	TSL:1 MANE Select	c.352+323G>A		intron	N/A	ENSP00000287814.4
	SYN2	ENST00000620175.4	TSL:1	c.775-5049C>T		intron	N/A	ENSP00000484916.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142429 AN: 152180 Hom.: 66737 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.936 AC: 142548 AN: 152298 Hom.: 66797 Cov.: 32 AF XY: 0.939 AC XY: 69908 AN XY: 74470

African (AFR) AF: 0.975 AC: 40532 AN: 41564

American (AMR) AF: 0.944 AC: 14437 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3289 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 0.950 AC: 4580 AN: 4820

European-Finnish (FIN) AF: 0.937 AC: 9944 AN: 10616

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61455 AN: 68024

Other (OTH) AF: 0.945 AC: 1997 AN: 2114

Alfa AF: 0.918 Hom.: 24100

Bravo AF: 0.939

Asia WGS AF: 0.975 AC: 3388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.7
DANN	Benign	0.66
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs308953; hg19: chr3-12197997;