Genetic Variant STX1A:c.31-1811C>T (chr7-73710933-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004603.4(STX1A):c.31-1811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,094 control chromosomes in the GnomAD database, including 6,560 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 0.28 ( 6560 hom., cov: 32)

Consequence

STX1A
NM_004603.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0290

Publications

12 publications found

Variant links:

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

STX1A links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STX1A	NM_004603.4 link	c.31-1811C>T	intron_variant	Intron 1 of 9	ENST00000222812.8	NP_004594.1	Q16623-1Q75ME0
STX1A	NM_001165903.2 link	c.31-1811C>T	intron_variant	Intron 1 of 9		NP_001159375.1	Q16623-3
STX1A	XM_047420777.1 link	c.31-1811C>T	intron_variant	Intron 1 of 8		XP_047276733.1
STX1A	XM_047420778.1 link	c.31-1811C>T	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 link	c.31-1811C>T		intron_variant	Intron 1 of 9	1	NM_004603.4	ENSP00000222812.3		Q16623-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42103

AN:

151976

Hom.:

6563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.271

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

GnomAD4 genome

AF:

0.277

AC:

42117

AN:

152094

Hom.:

6560

Cov.:

AF XY:

0.280

AC XY:

20832

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.129

AC:

5357

AN:

41536

American (AMR)

AF:

0.316

AC:

4826

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

865

AN:

3468

East Asian (EAS)

AF:

0.157

AC:

810

AN:

5164

South Asian (SAS)

AF:

0.362

AC:

1742

AN:

4814

European-Finnish (FIN)

AF:

0.417

AC:

4404

AN:

10558

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23248

AN:

67962

Other (OTH)

AF:

0.272

AC:

573

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1532

3063

4595

6126

7658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.299

Hom.:

1220

Bravo

AF:

0.259

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.7

(source)

DANN

Benign

0.58

PhyloP100

-0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over