rs17073498

Positions:

chr6-144186773-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003764.4(STX11):c.146G>A(p.Arg49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,613,978 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 86 hom. )

Consequence

STX11
NM_003764.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

STX11 (HGNC:11429): (syntaxin 11) This gene encodes a member of the syntaxin family. Syntaxins have been implicated in the targeting and fusion of intracellular transport vesicles. This family member may regulate protein transport among late endosomes and the trans-Golgi network. Mutations in this gene have been associated with familial hemophagocytic lymphohistiocytosis. [provided by RefSeq, Jul 2008]

STX11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014668703).

BP6

Variant 6-144186773-G-A is Benign according to our data. Variant chr6-144186773-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-144186773-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX11	NM_003764.4 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	2/2	ENST00000367568.5	NP_003755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
STX11	ENST00000367568.5 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	2/2	1	NM_003764.4	ENSP00000356540	P1
STX11	ENST00000698355.1 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	3/3			ENSP00000513678	P1
STX11	ENST00000698356.1 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	4/4			ENSP00000513679	P1
STX11	ENST00000698357.1 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	2/2			ENSP00000513680	P1

Frequencies

GnomAD3 genomes

AF:

0.00812

AC:

1235

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0634

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00707

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00749

AC:

1880

AN:

250930

Hom.:

AF XY:

0.00665

AC XY:

903

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0649

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.00689

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00283

AC:

4141

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

2023

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0541

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.00672

Gnomad4 NFE exome

AF:

0.000194

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00812

AC:

1237

AN:

152296

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

607

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0633

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00707

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00838

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00753

AC:

914

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hemophagocytic lymphohistiocytosis 4

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 07, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 18, 2022	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 23, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

3.2

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.051

MVP

0.24

MPC

0.42

ClinPred

0.0019

GERP RS

2.0

Varity_R

0.047

gMVP

0.12

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