NM_004603.4:c.678+171C>T

Variant names:

• chr7-73702674-G-A
• rs151012188
• NM_004603.4:c.678+171C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1A	NM_004603.4	c.678+171C>T		intron_variant	Intron 8 of 9	ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.678+171C>T		intron_variant	Intron 8 of 9		NP_001159375.1
STX1A	XM_047420777.1	c.793+56C>T		intron_variant	Intron 8 of 8		XP_047276733.1
STX1A	XM_047420778.1	c.678+171C>T		intron_variant	Intron 8 of 8		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.678+171C>T		intron_variant	Intron 8 of 9	1	NM_004603.4	ENSP00000222812.3

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

African (AFR) AF: 0.00162 AC: 49 AN: 30320

American (AMR) AF: 0.00579 AC: 170 AN: 29360

Ashkenazi Jewish (ASJ) AF: 0.00582 AC: 120 AN: 20634

East Asian (EAS) AF: 0.00 AC: 0 AN: 35384

South Asian (SAS) AF: 0.00100 AC: 69 AN: 68866

European-Finnish (FIN) AF: 0.0105 AC: 446 AN: 42316

Middle Eastern (MID) AF: 0.00777 AC: 29 AN: 3732

European-Non Finnish (NFE) AF: 0.00846 AC: 8832 AN: 1043706

Other (OTH) AF: 0.00660 AC: 363 AN: 55010

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

African (AFR) AF: 0.00137 AC: 57 AN: 41554

American (AMR) AF: 0.00673 AC: 103 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68016

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00496 Hom.: 2

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

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs151012188; hg19: chr7-73117004;