7-73700781-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The ENST00000395156.7(STX1A):c.692G>A(p.Gly231Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STX1A
ENST00000395156.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.114

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 3 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.3989 (below the threshold of 3.09). Trascript score misZ: 2.6361 (below the threshold of 3.09). GenCC associations: The gene is linked to cystic fibrosis, complex neurodevelopmental disorder, neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.0725722).

BP6

Variant 7-73700781-C-T is Benign according to our data. Variant chr7-73700781-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3802740.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1A	NM_004603.4 link	c.738G>A	p.Arg246Arg	synonymous_variant	Exon 9 of 10	ENST00000222812.8	NP_004594.1	Q16623-1Q75ME0
STX1A	NM_001165903.2 link	c.692G>A	p.Gly231Glu	missense_variant	Exon 9 of 10		NP_001159375.1	Q16623-3
STX1A	XM_047420777.1 link	c.*101G>A		3_prime_UTR_variant	Exon 9 of 9		XP_047276733.1
STX1A	XM_047420778.1 link	c.*46G>A		3_prime_UTR_variant	Exon 9 of 9		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8 link	c.738G>A	p.Arg246Arg	synonymous_variant	Exon 9 of 10	1	NM_004603.4	ENSP00000222812.3		Q16623-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251390

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Feb 06, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.4

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.23

M_CAP

Benign

0.0033

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

PhyloP100

-0.11

PROVEAN

Benign

-0.050

REVEL

Benign

0.063

Sift

Benign

0.25

Sift4G

Benign

0.095

Polyphen

0.0

Vest4

0.27

MVP

0.40

ClinPred

0.087

GERP RS

-0.75

Mutation Taster

=84/16

polymorphism

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over