Variant 17-9505058-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004853.3(STX8):c.428A>T(p.Gln143Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STX8
NM_004853.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
STX8	NM_004853.3 linkuse as main transcript	c.428A>T	p.Gln143Leu	missense_variant	5/8	ENST00000306357.9	NP_004844.1
STX8	XM_011524079.2 linkuse as main transcript	c.263A>T	p.Gln88Leu	missense_variant	3/6		XP_011522381.1
STX8	NR_033656.2 linkuse as main transcript	n.234A>T		non_coding_transcript_exon_variant	3/6
STX8	XR_934120.3 linkuse as main transcript	n.440A>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
STX8	ENST00000306357.9 linkuse as main transcript	c.428A>T	p.Gln143Leu	missense_variant	5/8	1	NM_004853.3	ENSP00000305255	P1
STX8	ENST00000574431.5 linkuse as main transcript	c.95A>T	p.Gln32Leu	missense_variant	4/7	3		ENSP00000467749
STX8	ENST00000575294.6 linkuse as main transcript	c.118-13137A>T		intron_variant, NMD_transcript_variant		5		ENSP00000468093
STX8	ENST00000575858.5 linkuse as main transcript	c.*87A>T		3_prime_UTR_variant, NMD_transcript_variant	3/6	3		ENSP00000460355

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151696

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.428A>T (p.Q143L) alteration is located in exon 5 (coding exon 5) of the STX8 gene. This alteration results from a A to T substitution at nucleotide position 428, causing the glutamine (Q) at amino acid position 143 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0087

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.3

D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.14

T;D

Polyphen

0.87

P;.

Vest4

0.57

MVP

0.42

MPC

0.15

ClinPred

0.92

GERP RS

5.7

Varity_R

0.56

gMVP

0.65

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

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