rs6609534

Variant names:

• chrX-47587254-G-A
• rs6609534
• NM_006950.3:c.775-9753C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-47587254-G-A
• chrX-47587254-G-T

Variant summary

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

The NM_006950.3(SYN1):​c.775-9753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 111,453 control chromosomes in the GnomAD database, including 3,598 homozygotes. There are 9,702 hemizygotes in GnomAD. 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 0.29 (3598 hom., 9702 hem., cov: 23)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 3 publications found

Genes affected

SYN1 (HGNC:11494): (synapsin I) 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 plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ENSG00000283743 (HGNC:):

MIR4769 (HGNC:41694): (microRNA 4769) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3	c.775-9753C>T		intron_variant	Intron 5 of 12	ENST00000295987.13	NP_008881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.775-9753C>T		intron_variant	Intron 5 of 12	2	NM_006950.3	ENSP00000295987.7
SYN1	ENST00000340666.5	c.775-9753C>T		intron_variant	Intron 5 of 12	1		ENSP00000343206.4
ENSG00000283743	ENST00000638776.2	n.3231-9753C>T		intron_variant	Intron 11 of 15	5
MIR4769	ENST00000584126.1	n.-175G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.289 AC: 32171 AN: 111397 Hom.: 3596 Cov.: 23

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.289 AC: 32179 AN: 111453 Hom.: 3598 Cov.: 23 AF XY: 0.288 AC XY: 9702 AN XY: 33713

African (AFR) AF: 0.149 AC: 4585 AN: 30750

American (AMR) AF: 0.263 AC: 2783 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 951 AN: 2643

East Asian (EAS) AF: 0.411 AC: 1421 AN: 3454

South Asian (SAS) AF: 0.460 AC: 1228 AN: 2667

European-Finnish (FIN) AF: 0.346 AC: 2074 AN: 5998

Middle Eastern (MID) AF: 0.274 AC: 59 AN: 215

European-Non Finnish (NFE) AF: 0.348 AC: 18394 AN: 52919

Other (OTH) AF: 0.288 AC: 442 AN: 1537

Alfa AF: 0.302 Hom.: 2734

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.80
PhyloP100		0.82
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: rs6609534; hg19: chrX-47446653;