rs3793243

Variant names:

• chr7-73707017-A-G
• rs3793243
• NM_004603.4:c.208+1572T>C

Variant summary

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

The NM_004603.4(STX1A):​c.208+1572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,938 control chromosomes in the GnomAD database, including 22,800 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 0.55 (22800 hom., cov: 31)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 19 publications found

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]

STX1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1A	NM_004603.4	c.208+1572T>C		intron_variant	Intron 3 of 9	ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.208+1572T>C		intron_variant	Intron 3 of 9		NP_001159375.1
STX1A	XM_047420777.1	c.208+1572T>C		intron_variant	Intron 3 of 8		XP_047276733.1
STX1A	XM_047420778.1	c.208+1572T>C		intron_variant	Intron 3 of 8		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.208+1572T>C		intron_variant	Intron 3 of 9	1	NM_004603.4	ENSP00000222812.3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82825 AN: 151820 Hom.: 22784 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.545 AC: 82880 AN: 151938 Hom.: 22800 Cov.: 31 AF XY: 0.540 AC XY: 40097 AN XY: 74240

African (AFR) AF: 0.524 AC: 21724 AN: 41450

American (AMR) AF: 0.490 AC: 7484 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2270 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2225 AN: 5122

South Asian (SAS) AF: 0.428 AC: 2061 AN: 4814

European-Finnish (FIN) AF: 0.527 AC: 5558 AN: 10556

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39648 AN: 67954

Other (OTH) AF: 0.563 AC: 1185 AN: 2106

Alfa AF: 0.573 Hom.: 60368

Bravo AF: 0.546

Asia WGS AF: 0.416 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3793243; hg19: chr7-73121347;