Variant chr17-9505091-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004853.3(STX8):c.395C>T(p.Thr132Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

STX8
NM_004853.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40214813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
STX8	NM_004853.3 linkuse as main transcript	c.395C>T	p.Thr132Ile	missense_variant	5/8	ENST00000306357.9	NP_004844.1
STX8	XM_011524079.2 linkuse as main transcript	c.230C>T	p.Thr77Ile	missense_variant	3/6		XP_011522381.1
STX8	NR_033656.2 linkuse as main transcript	n.201C>T		non_coding_transcript_exon_variant	3/6
STX8	XR_934120.3 linkuse as main transcript	n.407C>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.395C>T	p.Thr132Ile	missense_variant	5/8	1	NM_004853.3	ENSP00000305255	P1
STX8	ENST00000574431.5 linkuse as main transcript	c.62C>T	p.Thr21Ile	missense_variant	4/7	3		ENSP00000467749
STX8	ENST00000575294.6 linkuse as main transcript	c.118-13170C>T		intron_variant, NMD_transcript_variant		5		ENSP00000468093
STX8	ENST00000575858.5 linkuse as main transcript	c.*54C>T		3_prime_UTR_variant, NMD_transcript_variant	3/6	3		ENSP00000460355

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

May 27, 2022

The c.395C>T (p.T132I) alteration is located in exon 5 (coding exon 5) of the STX8 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the threonine (T) at amino acid position 132 to be replaced by an isoleucine (I). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.21

Sift

Uncertain

0.0060

D;.

Sift4G

Benign

0.080

T;T

Polyphen

0.99

D;.

Vest4

0.48

MutPred

0.39

Loss of phosphorylation at T132 (P = 0.0155);.;

MVP

0.62

MPC

0.22

ClinPred

0.98

GERP RS

4.8

Varity_R

0.36

gMVP

0.79

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