rs45574234

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003764.4(STX11):c.799G>A(p.Val267Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,611,770 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V267V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0054 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 52 hom. )

Consequence

STX11
NM_003764.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.74

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

familial hemophagocytic lymphohistiocytosis 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
hereditary hemophagocytic lymphohistiocytosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

STX11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009943932).

BP6

Variant 6-144187426-G-A is Benign according to our data. Variant chr6-144187426-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00542 (826/152300) while in subpopulation NFE AF = 0.00908 (618/68030). AF 95% confidence interval is 0.00849. There are 11 homozygotes in GnomAd4. There are 399 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003764.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX11	NM_003764.4	MANE Select	c.799G>A	p.Val267Met	missense	Exon 2 of 2	NP_003755.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX11	ENST00000367568.5	TSL:1 MANE Select	c.799G>A	p.Val267Met	missense	Exon 2 of 2	ENSP00000356540.4	O75558
STX11	ENST00000698355.1		c.799G>A	p.Val267Met	missense	Exon 3 of 3	ENSP00000513678.1	O75558
STX11	ENST00000698356.1		c.799G>A	p.Val267Met	missense	Exon 4 of 4	ENSP00000513679.1	O75558

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00908

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00532

AC:

1314

AN:

247122

AF XY:

0.00538

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00452

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.00810

Gnomad OTH exome

AF:

0.00740

GnomAD4 exome

AF:

0.00705

AC:

10288

AN:

1459470

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

5081

AN XY:

726188

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33476

American (AMR)

AF:

0.00474

AC:

212

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39696

South Asian (SAS)

AF:

0.00321

AC:

277

AN:

86258

European-Finnish (FIN)

AF:

0.00329

AC:

168

AN:

51110

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00817

AC:

9082

AN:

1111938

Other (OTH)

AF:

0.00672

AC:

406

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

688

1376

2064

2752

3440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00542

AC:

826

AN:

152300

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41576

American (AMR)

AF:

0.00608

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00908

AC:

618

AN:

68030

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00709

Hom.:

Bravo

AF:

0.00543

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00549

AC:

667

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00735

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial hemophagocytic lymphohistiocytosis 4 (3)

not provided (3)

not specified (2)

Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

M_CAP

Benign

0.021

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.6

PhyloP100

2.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.7

REVEL

Benign

0.26

Sift

Benign

0.036

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.089

MVP

0.72

MPC

1.0

ClinPred

0.012

GERP RS

2.9

Varity_R

0.12

gMVP

0.30

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over