rs2228607

chr7-73708593-A-Gchr7-73708593-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004603.4(STX1A):c.204T>C(p.Asp68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,612,352 control chromosomes in the GnomAD database, including 239,418 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 0.53 (21310 hom., cov: 33)
  • Exomes 𝑓: 0.54 (218108 hom.)
• Consequence: STX1A NM_004603.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

Genes affected

STX1A (HGNC:11433): (syntaxin 1A) This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-3.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1A	NM_004603.4	c.204T>C	p.Asp68=	synonymous_variant	3/10	ENST00000222812.8
STX1A	NM_001165903.2	c.204T>C	p.Asp68=	synonymous_variant	3/10
STX1A	XM_047420777.1	c.204T>C	p.Asp68=	synonymous_variant	3/9
STX1A	XM_047420778.1	c.204T>C	p.Asp68=	synonymous_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1A	ENST00000222812.8	c.204T>C	p.Asp68=	synonymous_variant	3/10	1	NM_004603.4	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80031 AN: 152004 Hom.: 21294 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.515 AC: 127851 AN: 248296 Hom.: 33476 AF XY: 0.517 AC XY: 69448 AN XY: 134338

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.429

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.523

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.544 AC: 794674 AN: 1460230 Hom.: 218108 Cov.: 43 AF XY: 0.542 AC XY: 393799 AN XY: 726334

Gnomad4 AFR exome AF: 0.507

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.526 AC: 80089 AN: 152122 Hom.: 21310 Cov.: 33 AF XY: 0.523 AC XY: 38864 AN XY: 74354

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.544

Alfa AF: 0.556 Hom.: 12005

Bravo AF: 0.525

Asia WGS AF: 0.411 AC: 1431 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.37
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2228607; hg19: chr7-73122923; COSMIC: COSV56109559; COSMIC: COSV56109559;