Variant 17-9575803-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004853.3(STX8):c.6A>G(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,541,636 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 29 hom. )

Consequence

STX8
NM_004853.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.71

Variant links:

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]

STX8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-9575803-T-C is Benign according to our data. Variant chr17-9575803-T-C is described in ClinVar as [Benign]. Clinvar id is 786305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0083 (1262/152016) while in subpopulation AFR AF= 0.0292 (1212/41480). AF 95% confidence interval is 0.0279. There are 19 homozygotes in gnomad4. There are 575 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
STX8	NM_004853.3 linkuse as main transcript	c.6A>G	p.Ala2=	synonymous_variant	1/8	ENST00000306357.9	NP_004844.1
STX8	NR_033656.2 linkuse as main transcript	n.18A>G		non_coding_transcript_exon_variant	1/6
STX8	XR_934120.3 linkuse as main transcript	n.18A>G		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX8	ENST00000306357.9 linkuse as main transcript	c.6A>G	p.Ala2=	synonymous_variant	1/8	1	NM_004853.3	ENSP00000305255	P1

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1260

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00184

AC:

263

AN:

142630

Hom.:

AF XY:

0.00122

AC XY:

AN XY:

76476

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.000902

AC:

1254

AN:

1389620

Hom.:

Cov.:

AF XY:

0.000776

AC XY:

532

AN XY:

685754

show subpopulations

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00830

AC:

1262

AN:

152016

Hom.:

Cov.:

AF XY:

0.00774

AC XY:

575

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00994

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.9

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over