7-73702674-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004603.4(STX1A):c.678+171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,481,612 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (41 hom.)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-73702674-G-A is Benign according to our data. Variant chr7-73702674-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 949 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1A	NM_004603.4	c.678+171C>T		intron_variant		ENST00000222812.8
STX1A	NM_001165903.2	c.678+171C>T		intron_variant
STX1A	XM_047420777.1	c.793+56C>T		intron_variant
STX1A	XM_047420778.1	c.678+171C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1A	ENST00000222812.8	c.678+171C>T		intron_variant		1	NM_004603.4	P1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 949 AN: 152166 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00758 AC: 10078 AN: 1329328 Hom.: 41 Cov.: 31 AF XY: 0.00738 AC XY: 4769 AN XY: 646598

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00579

Gnomad4 ASJ exome AF: 0.00582

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.00846

Gnomad4 OTH exome AF: 0.00660

GnomAD4 genome AF: 0.00623 AC: 949 AN: 152284 Hom.: 3 Cov.: 32 AF XY: 0.00623 AC XY: 464 AN XY: 74454

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.00816

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00635 Hom.: 0

Bravo AF: 0.00579

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

STX1A: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	11
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs151012188; hg19: chr7-73117004;