rs3757299

chr6-132464085-A-C

Variant summary

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

The NM_003569.3(STX7):c.611-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,610,954 control chromosomes in the GnomAD database, including 38,582 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 0.21 (3333 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35249 hom.)
• Consequence: STX7 NM_003569.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.1601
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

Genes affected

STX7 (HGNC:11442): (syntaxin 7) The protein encoded by this gene is a syntaxin family membrane receptor involved in vesicle transport. The encoded protein binds alpha-SNAP, an important regulator of transport vesicle fusion. Along with syntaxin 13, this protein plays a role in the ordered fusion of endosomes and lysosomes with the phagosome. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX7	NM_003569.3	c.611-10T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000367941.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX7	ENST00000367941.7	c.611-10T>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003569.3	P1
STX7	ENST00000367937.4	c.611-10T>G		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31552 AN: 152046 Hom.: 3329 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.213 AC: 53406 AN: 250322 Hom.: 5937 AF XY: 0.216 AC XY: 29217 AN XY: 135278

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.218 AC: 318663 AN: 1458790 Hom.: 35249 Cov.: 31 AF XY: 0.220 AC XY: 159865 AN XY: 725900

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.207 AC: 31556 AN: 152164 Hom.: 3333 Cov.: 32 AF XY: 0.206 AC XY: 15295 AN XY: 74390

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.207

Alfa AF: 0.212 Hom.: 1321

Bravo AF: 0.211

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	19
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.16
dbscSNV1_RF	Benign	0.49
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: rs3757299; hg19: chr6-132785224; COSMIC: COSV63398205;