7-73708626-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004603.4(STX1A):​c.171G>A​(p.Lys57Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

STX1A
NM_004603.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.575
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 7-73708626-C-T is Benign according to our data. Variant chr7-73708626-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3771342.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.575 with no splicing effect.
BS2
High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STX1ANM_004603.4 linkc.171G>A p.Lys57Lys synonymous_variant Exon 3 of 10 ENST00000222812.8 NP_004594.1 Q16623-1Q75ME0
STX1ANM_001165903.2 linkc.171G>A p.Lys57Lys synonymous_variant Exon 3 of 10 NP_001159375.1 Q16623-3
STX1AXM_047420777.1 linkc.171G>A p.Lys57Lys synonymous_variant Exon 3 of 9 XP_047276733.1
STX1AXM_047420778.1 linkc.171G>A p.Lys57Lys synonymous_variant Exon 3 of 9 XP_047276734.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STX1AENST00000222812.8 linkc.171G>A p.Lys57Lys synonymous_variant Exon 3 of 10 1 NM_004603.4 ENSP00000222812.3 Q16623-1

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152252
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00132
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000307
AC:
77
AN:
251078
Hom.:
0
AF XY:
0.000295
AC XY:
40
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00181
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000298
AC:
436
AN:
1461818
Hom.:
1
Cov.:
35
AF XY:
0.000287
AC XY:
209
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000243
Gnomad4 FIN exome
AF:
0.00137
Gnomad4 NFE exome
AF:
0.000280
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152370
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00132
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000245
Hom.:
0
Bravo
AF:
0.000178
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

STX1A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
8.8
DANN
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs140052001; hg19: chr7-73122956; API