chr17-9433147-G-C

Variant names:

• chr17-9433147-G-C
• rs7211026
• NM_004853.3:c.542-54494C>G

Variant summary

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

The NM_004853.3(STX8):​c.542-54494C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,148 control chromosomes in the GnomAD database, including 2,740 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 0.11 (2740 hom., cov: 33)
• Consequence: STX8 NM_004853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 1 publications found

Genes affected

STX8 (HGNC:11443): (syntaxin 8) The gene is a member of the syntaxin family. The encoded protein is involved in protein trafficking from early to late endosomes via vesicle fusion and exocytosis. A related pseudogene has been identified on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX8	NM_004853.3	c.542-54494C>G		intron_variant	Intron 6 of 7	ENST00000306357.9	NP_004844.1
STX8	NR_033656.2	n.348-54494C>G		intron_variant	Intron 4 of 5
STX8	XM_011524079.2	c.377-54494C>G		intron_variant	Intron 4 of 5		XP_011522381.1
STX8	XR_934120.3	n.644+4650C>G		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX8	ENST00000306357.9	c.542-54494C>G		intron_variant	Intron 6 of 7	1	NM_004853.3	ENSP00000305255.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16712 AN: 152030 Hom.: 2728 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.0981

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16760 AN: 152148 Hom.: 2740 Cov.: 33 AF XY: 0.106 AC XY: 7866 AN XY: 74390

African (AFR) AF: 0.356 AC: 14757 AN: 41446

American (AMR) AF: 0.0519 AC: 794 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.0594 AC: 307 AN: 5172

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00360 AC: 245 AN: 68018

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.00412 Hom.: 10

Bravo AF: 0.125

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7211026; hg19: chr17-9336464; COSMIC: COSV60494186;