Variant 7-73708647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004603.4(STX1A):c.150C>T(p.Asn50Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,613,994 control chromosomes in the GnomAD database, including 6,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.085 ( 578 hom., cov: 33)

Exomes 𝑓: 0.086 ( 5741 hom. )

Consequence

STX1A
NM_004603.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.157

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 links:

STX1A (HGNC:):

STX1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-73708647-G-A is Benign according to our data. Variant chr7-73708647-G-A is described in ClinVar as [Benign]. Clinvar id is 3056826.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.157 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1A	NM_004603.4 linkuse as main transcript	c.150C>T	p.Asn50Asn	synonymous_variant	3/10	ENST00000222812.8	NP_004594.1	Q16623-1Q75ME0
STX1A	NM_001165903.2 linkuse as main transcript	c.150C>T	p.Asn50Asn	synonymous_variant	3/10		NP_001159375.1	Q16623-3
STX1A	XM_047420777.1 linkuse as main transcript	c.150C>T	p.Asn50Asn	synonymous_variant	3/9		XP_047276733.1
STX1A	XM_047420778.1 linkuse as main transcript	c.150C>T	p.Asn50Asn	synonymous_variant	3/9		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8 linkuse as main transcript	c.150C>T	p.Asn50Asn	synonymous_variant	3/10	1	NM_004603.4	ENSP00000222812.3		Q16623-1

Frequencies

GnomAD3 genomes

AF:

0.0856

AC:

13019

AN:

152164

Hom.:

578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0857

Gnomad ASJ

AF:

0.0949

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.0613

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0910

Gnomad OTH

AF:

0.0993

GnomAD3 exomes

AF:

0.0733

AC:

18403

AN:

250970

Hom.:

783

AF XY:

0.0746

AC XY:

10128

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0928

Gnomad AMR exome

AF:

0.0546

Gnomad ASJ exome

AF:

0.0917

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0567

Gnomad FIN exome

AF:

0.0622

Gnomad NFE exome

AF:

0.0922

Gnomad OTH exome

AF:

0.0901

GnomAD4 exome

AF:

0.0859

AC:

125540

AN:

1461712

Hom.:

5741

Cov.:

AF XY:

0.0854

AC XY:

62128

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.0584

Gnomad4 ASJ exome

AF:

0.0905

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0583

Gnomad4 FIN exome

AF:

0.0617

Gnomad4 NFE exome

AF:

0.0928

Gnomad4 OTH exome

AF:

0.0871

GnomAD4 genome

AF:

0.0855

AC:

13020

AN:

152282

Hom.:

578

Cov.:

AF XY:

0.0837

AC XY:

6235

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0934

Gnomad4 AMR

AF:

0.0856

Gnomad4 ASJ

AF:

0.0949

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0555

Gnomad4 FIN

AF:

0.0613

Gnomad4 NFE

AF:

0.0910

Gnomad4 OTH

AF:

0.0983

Alfa

AF:

0.0900

Hom.:

327

Bravo

AF:

0.0888

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

EpiCase

AF:

0.101

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

STX1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.7

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over