rs6951030

Variant names:

• chr7-73718911-T-G
• rs6951030
• NM_004603.4:c.30+691A>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.30+691A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,268 control chromosomes in the GnomAD database, including 3,598 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 0.21 (3598 hom., cov: 31)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 22 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1A	NM_004603.4	c.30+691A>C		intron_variant	Intron 1 of 9	ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.30+691A>C		intron_variant	Intron 1 of 9		NP_001159375.1
STX1A	XM_047420777.1	c.30+691A>C		intron_variant	Intron 1 of 8		XP_047276733.1
STX1A	XM_047420778.1	c.30+691A>C		intron_variant	Intron 1 of 8		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.30+691A>C		intron_variant	Intron 1 of 9	1	NM_004603.4	ENSP00000222812.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31194 AN: 151152 Hom.: 3591 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.207 AC: 31237 AN: 151268 Hom.: 3598 Cov.: 31 AF XY: 0.202 AC XY: 14907 AN XY: 73872

African (AFR) AF: 0.313 AC: 12894 AN: 41168

American (AMR) AF: 0.151 AC: 2303 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3460

East Asian (EAS) AF: 0.0439 AC: 222 AN: 5056

South Asian (SAS) AF: 0.115 AC: 552 AN: 4788

European-Finnish (FIN) AF: 0.163 AC: 1709 AN: 10504

Middle Eastern (MID) AF: 0.252 AC: 73 AN: 290

European-Non Finnish (NFE) AF: 0.177 AC: 12024 AN: 67760

Other (OTH) AF: 0.211 AC: 444 AN: 2106

Alfa AF: 0.185 Hom.: 10166

Bravo AF: 0.209

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.66
PhyloP100		0.29
Mutation Taster		=94/6	polymorphism (auto)

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: rs6951030; hg19: chr7-73133241;