rs4363087

Variant names:

• chr7-73703866-T-C
• rs4363087
• NM_004603.4:c.467-38A>G

Variant summary

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

The NM_004603.4(STX1A):​c.467-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,599,828 control chromosomes in the GnomAD database, including 132,502 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 0.33 (10005 hom., cov: 32)
  • Exomes 𝑓: 0.40 (122497 hom.)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 10 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):

• neurodevelopmental disorder

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P
• complex neurodevelopmental disorder

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC105375350 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004603.4. 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
	STX1A	NM_004603.4	MANE Select	c.467-38A>G		intron	N/A	NP_004594.1	Q75ME0
	STX1A	NM_001165903.2		c.467-38A>G		intron	N/A	NP_001159375.1	Q16623-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX1A	ENST00000222812.8	TSL:1 MANE Select	c.467-38A>G		intron	N/A	ENSP00000222812.3	Q16623-1
	STX1A	ENST00000395156.7	TSL:1	c.467-38A>G		intron	N/A	ENSP00000378585.3	Q16623-3
	STX1A	ENST00000929307.1		c.467-38A>G		intron	N/A	ENSP00000599366.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50385 AN: 151924 Hom.: 10007 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.336

GnomAD2 exomes AF: 0.421 AC: 99554 AN: 236522 AF XY: 0.426

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.588

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.404 AC: 584194 AN: 1447786 Hom.: 122497 Cov.: 33 AF XY: 0.407 AC XY: 292734 AN XY: 719628

African (AFR) AF: 0.0932 AC: 3097 AN: 33238

American (AMR) AF: 0.489 AC: 21326 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7475 AN: 25228

East Asian (EAS) AF: 0.641 AC: 25379 AN: 39586

South Asian (SAS) AF: 0.522 AC: 44231 AN: 84802

European-Finnish (FIN) AF: 0.454 AC: 23329 AN: 51354

Middle Eastern (MID) AF: 0.204 AC: 1031 AN: 5056

European-Non Finnish (NFE) AF: 0.394 AC: 435643 AN: 1105138

Other (OTH) AF: 0.379 AC: 22683 AN: 59788

GnomAD4 genome AF: 0.331 AC: 50389 AN: 152042 Hom.: 10005 Cov.: 32 AF XY: 0.340 AC XY: 25292 AN XY: 74294

African (AFR) AF: 0.111 AC: 4625 AN: 41498

American (AMR) AF: 0.429 AC: 6555 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3034 AN: 5146

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4826

European-Finnish (FIN) AF: 0.459 AC: 4851 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26672 AN: 67960

Other (OTH) AF: 0.339 AC: 713 AN: 2102

Alfa AF: 0.350 Hom.: 1920

Bravo AF: 0.316

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.74
PhyloP100		0.019
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4363087; hg19: chr7-73118196; COSMIC: COSV56108886; COSMIC: COSV56108886;