17-9365185-T-C

Variant names:

• chr17-9365185-T-C
• rs4239104
• NM_004853.3:c.643+13367A>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.643+13367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 152,298 control chromosomes in the GnomAD database, including 867 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 0.094 (867 hom., cov: 33)
• Consequence: STX8 NM_004853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX8	NM_004853.3	c.643+13367A>G		intron_variant	Intron 7 of 7	ENST00000306357.9	NP_004844.1
STX8	NR_033656.2	n.449+13367A>G		intron_variant	Intron 5 of 5
STX8	XM_011524079.2	c.478+13367A>G		intron_variant	Intron 5 of 5		XP_011522381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX8	ENST00000306357.9	c.643+13367A>G		intron_variant	Intron 7 of 7	1	NM_004853.3	ENSP00000305255.2

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14321 AN: 152180 Hom.: 868 Cov.: 33

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0940 AC: 14318 AN: 152298 Hom.: 867 Cov.: 33 AF XY: 0.0987 AC XY: 7351 AN XY: 74470

African (AFR) AF: 0.0334 AC: 1389 AN: 41574

American (AMR) AF: 0.167 AC: 2548 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 769 AN: 3472

East Asian (EAS) AF: 0.127 AC: 660 AN: 5186

South Asian (SAS) AF: 0.0652 AC: 315 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10602

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6472 AN: 68022

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.102 Hom.: 1922

Bravo AF: 0.0969

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.86
PhyloP100		-1.0
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: rs4239104; hg19: chr17-9268502;