X-47606962-A-G

Variant names:

• chrX-47606962-A-G
• rs1142636
• NM_006950.3:c.510T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006950.3(SYN1):​c.510T>C​(p.Asn170Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,205,344 control chromosomes in the GnomAD database, including 59,194 homozygotes. There are 147,047 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (6121 hom., 11667 hem., cov: 21)
  • Exomes 𝑓: 0.38 (53073 hom. 135380 hem.)
• Consequence: SYN1 NM_006950.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.29
• Publications: 20 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]

SYN1 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, G2P
• intellectual disability, X-linked 50

  Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia

ENSG00000283743 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-47606962-A-G is Benign according to our data. Variant chrX-47606962-A-G is described in ClinVar as Benign. ClinVar VariationId is 96364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006950.3. 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
	SYN1	NM_006950.3	MANE Select	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	NP_008881.2	P17600-1
	SYN1	NM_133499.2		c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	NP_598006.1	P17600-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	ENST00000295987.13	TSL:2 MANE Select	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	ENSP00000295987.7	P17600-1
	SYN1	ENST00000340666.5	TSL:1	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	ENSP00000343206.4	P17600-2
	SYN1	ENST00000950906.1		c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	ENSP00000620965.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 42238 AN: 108421 Hom.: 6119 Cov.: 21

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.371 AC: 67286 AN: 181327 AF XY: 0.360

Gnomad AFR exome AF: 0.423

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.376 AC: 412886 AN: 1096885 Hom.: 53073 Cov.: 32 AF XY: 0.374 AC XY: 135380 AN XY: 362439

African (AFR) AF: 0.421 AC: 11115 AN: 26391

American (AMR) AF: 0.396 AC: 13891 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 7629 AN: 19372

East Asian (EAS) AF: 0.203 AC: 6126 AN: 30182

South Asian (SAS) AF: 0.320 AC: 17299 AN: 54063

European-Finnish (FIN) AF: 0.388 AC: 15679 AN: 40432

Middle Eastern (MID) AF: 0.368 AC: 1518 AN: 4130

European-Non Finnish (NFE) AF: 0.383 AC: 322150 AN: 841215

Other (OTH) AF: 0.380 AC: 17479 AN: 46032

GnomAD4 genome AF: 0.390 AC: 42256 AN: 108459 Hom.: 6121 Cov.: 21 AF XY: 0.379 AC XY: 11667 AN XY: 30819

African (AFR) AF: 0.421 AC: 12486 AN: 29643

American (AMR) AF: 0.396 AC: 3991 AN: 10087

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1030 AN: 2608

East Asian (EAS) AF: 0.254 AC: 871 AN: 3424

South Asian (SAS) AF: 0.306 AC: 762 AN: 2492

European-Finnish (FIN) AF: 0.370 AC: 2033 AN: 5497

Middle Eastern (MID) AF: 0.355 AC: 77 AN: 217

European-Non Finnish (NFE) AF: 0.385 AC: 20150 AN: 52361

Other (OTH) AF: 0.406 AC: 595 AN: 1465

Alfa AF: 0.389 Hom.: 18572

Bravo AF: 0.396

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (2)
-	-	2	not specified (2)
-	-	1	History of neurodevelopmental disorder (1)
-	-	1	Intellectual disability, X-linked 50 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		1.3
Mutation Taster		=99/1	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: rs1142636; hg19: chrX-47466361;