NM_004853.3:c.542-13339G>A

Variant names:

• chr17-9391992-C-T
• rs7219526
• NM_004853.3:c.542-13339G>A

Variant summary

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

The NM_004853.3(STX8):​c.542-13339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,014 control chromosomes in the GnomAD database, including 5,015 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 0.25 (5015 hom., cov: 32)
• Consequence: STX8 NM_004853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX8	NM_004853.3	c.542-13339G>A		intron_variant	Intron 6 of 7	ENST00000306357.9	NP_004844.1
STX8	NR_033656.2	n.348-13339G>A		intron_variant	Intron 4 of 5
STX8	XM_011524079.2	c.377-13339G>A		intron_variant	Intron 4 of 5		XP_011522381.1
STX8	XR_934120.3	n.645-13339G>A		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX8	ENST00000306357.9	c.542-13339G>A		intron_variant	Intron 6 of 7	1	NM_004853.3	ENSP00000305255.2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38120 AN: 151896 Hom.: 5004 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.251 AC: 38159 AN: 152014 Hom.: 5015 Cov.: 32 AF XY: 0.248 AC XY: 18419 AN XY: 74304

African (AFR) AF: 0.323 AC: 13386 AN: 41444

American (AMR) AF: 0.189 AC: 2881 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1115 AN: 5160

South Asian (SAS) AF: 0.201 AC: 967 AN: 4806

European-Finnish (FIN) AF: 0.210 AC: 2218 AN: 10566

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15993 AN: 67980

Other (OTH) AF: 0.240 AC: 505 AN: 2104

Alfa AF: 0.238 Hom.: 3389

Bravo AF: 0.255

Asia WGS AF: 0.210 AC: 730 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	0.69
DANN	Benign	0.79
PhyloP100		-0.99
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: rs7219526; hg19: chr17-9295309;