rs3757299

Variant names:

• chr6-132464085-A-C
• rs3757299
• NM_003569.3:c.611-10T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003569.3(STX7):​c.611-10T>G variant causes a 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 intron
• Scores: Splicing: ADA: 0.1601
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003569.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX7	NM_003569.3	MANE Select	c.611-10T>G		intron	N/A	NP_003560.2
	STX7	NM_001326578.2		c.611-10T>G		intron	N/A	NP_001313507.1
	STX7	NM_001326579.2		c.611-10T>G		intron	N/A	NP_001313508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX7	ENST00000367941.7	TSL:1 MANE Select	c.611-10T>G		intron	N/A	ENSP00000356918.1
	STX7	ENST00000367937.4	TSL:5	c.611-10T>G		intron	N/A	ENSP00000356914.4

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

GnomAD2 exomes AF: 0.213 AC: 53406 AN: 250322 AF XY: 0.216

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 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

African (AFR) AF: 0.216 AC: 7221 AN: 33418

American (AMR) AF: 0.220 AC: 9837 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6628 AN: 26104

East Asian (EAS) AF: 0.181 AC: 7192 AN: 39666

South Asian (SAS) AF: 0.267 AC: 23032 AN: 86154

European-Finnish (FIN) AF: 0.167 AC: 8875 AN: 53082

Middle Eastern (MID) AF: 0.278 AC: 1601 AN: 5756

European-Non Finnish (NFE) AF: 0.217 AC: 240794 AN: 1109620

Other (OTH) AF: 0.224 AC: 13483 AN: 60278

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

African (AFR) AF: 0.214 AC: 8904 AN: 41516

American (AMR) AF: 0.186 AC: 2850 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3470

East Asian (EAS) AF: 0.154 AC: 795 AN: 5178

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4818

European-Finnish (FIN) AF: 0.167 AC: 1775 AN: 10598

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14401 AN: 67992

Other (OTH) AF: 0.207 AC: 436 AN: 2106

Alfa AF: 0.213 Hom.: 1855

Bravo AF: 0.211

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.65
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3757299; hg19: chr6-132785224; COSMIC: COSV63398205;