rs146949718

Positions:

chr6-144187173-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_003764.4(STX11):c.546G>A(p.Glu182=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00273 in 1,613,996 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 33 hom. )

Consequence

STX11
NM_003764.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.82

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 6-144187173-G-A is Benign according to our data. Variant chr6-144187173-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-144187173-G-A is described in Lovd as [Likely_benign]. Variant chr6-144187173-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00303 (462/152336) while in subpopulation SAS AF= 0.0089 (43/4830). AF 95% confidence interval is 0.00679. There are 3 homozygotes in gnomad4. There are 247 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX11	NM_003764.4 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_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.546G>A	p.Glu182=	synonymous_variant	2/2	1	NM_003764.4	ENSP00000356540	P1
STX11	ENST00000698355.1 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_variant	3/3			ENSP00000513678	P1
STX11	ENST00000698356.1 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_variant	4/4			ENSP00000513679	P1
STX11	ENST00000698357.1 linkuse as main transcript	c.546G>A	p.Glu182=	synonymous_variant	2/2			ENSP00000513680	P1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00403

AC:

1011

AN:

250888

Hom.:

AF XY:

0.00484

AC XY:

657

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00270

AC:

3947

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2255

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00303

AC:

462

AN:

152336

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00257

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.00301

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	STX11: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Familial hemophagocytic lymphohistiocytosis 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.0

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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