chr7-73700151-C-T

Position:

• chr7-73700151-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000222812.8(STX1A):​c.*256G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 563,168 control chromosomes in the GnomAD database, including 2,230 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 0.099 (941 hom., cov: 32)
  • Exomes 𝑓: 0.072 (1289 hom.)
• Consequence: STX1A ENST00000222812.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1A	NM_004603.4	c.*256G>A		3_prime_UTR_variant	10/10	ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.*321G>A		3_prime_UTR_variant	10/10		NP_001159375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.*256G>A		3_prime_UTR_variant	10/10	1	NM_004603.4	ENSP00000222812	P1
STX1A	ENST00000395156.7	c.*321G>A		3_prime_UTR_variant	10/10	1		ENSP00000378585
STX1A	ENST00000484736.5	n.536G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14993 AN: 152072 Hom.: 934 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0724 AC: 29775 AN: 410978 Hom.: 1289 Cov.: 3 AF XY: 0.0729 AC XY: 15779 AN XY: 216400

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0776

Gnomad4 EAS exome AF: 0.0212

Gnomad4 SAS exome AF: 0.0763

Gnomad4 FIN exome AF: 0.0447

Gnomad4 NFE exome AF: 0.0709

Gnomad4 OTH exome AF: 0.0860

GnomAD4 genome AF: 0.0987 AC: 15016 AN: 152190 Hom.: 941 Cov.: 32 AF XY: 0.0976 AC XY: 7265 AN XY: 74412

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.0874 Hom.: 464

Bravo AF: 0.109

Asia WGS AF: 0.0640 AC: 224 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	6.4
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs1569061; hg19: chr7-73114481;