X-47587120-T-G

Position:

• chrX-47587120-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006950.3(SYN1):​c.775-9619A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 111,830 control chromosomes in the GnomAD database, including 7,745 homozygotes. There are 14,920 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 0.44 (7745 hom., 14920 hem., cov: 24)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN1	NM_006950.3	c.775-9619A>C		intron_variant		ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2	c.775-9619A>C		intron_variant			NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.775-9619A>C		intron_variant		2	NM_006950.3	ENSP00000295987	P3
SYN1	ENST00000340666.5	c.775-9619A>C		intron_variant		1		ENSP00000343206	A1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 49438 AN: 111774 Hom.: 7736 Cov.: 24 AF XY: 0.438 AC XY: 14890 AN XY: 33986

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.442 AC: 49478 AN: 111830 Hom.: 7745 Cov.: 24 AF XY: 0.438 AC XY: 14920 AN XY: 34052

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.446

Alfa AF: 0.447 Hom.: 20491

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.81

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: rs2070584; hg19: chrX-47446519;