6-144186648-ACTT-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_SupportingBS1_Supporting

The NM_003764.4(STX11):​c.24_26delTCT​(p.Leu9del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

STX11
NM_003764.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 7.45
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_003764.4. Strenght limited to Supporting due to length of the change: 1aa.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000276 (42/152214) while in subpopulation NFE AF = 0.000529 (36/68036). AF 95% confidence interval is 0.000392. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STX11NM_003764.4 linkc.24_26delTCT p.Leu9del disruptive_inframe_deletion Exon 2 of 2 ENST00000367568.5 NP_003755.2 O75558

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STX11ENST00000367568.5 linkc.24_26delTCT p.Leu9del disruptive_inframe_deletion Exon 2 of 2 1 NM_003764.4 ENSP00000356540.4 O75558
STX11ENST00000698355.1 linkc.24_26delTCT p.Leu9del disruptive_inframe_deletion Exon 3 of 3 ENSP00000513678.1 O75558
STX11ENST00000698356.1 linkc.24_26delTCT p.Leu9del disruptive_inframe_deletion Exon 4 of 4 ENSP00000513679.1 O75558
STX11ENST00000698357.1 linkc.24_26delTCT p.Leu9del disruptive_inframe_deletion Exon 2 of 2 ENSP00000513680.1 O75558

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
42
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.000956
GnomAD2 exomes
AF:
0.000211
AC:
53
AN:
251272
AF XY:
0.000177
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000361
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000426
AC:
622
AN:
1461804
Hom.:
0
AF XY:
0.000407
AC XY:
296
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
AC:
3
AN:
33480
Gnomad4 AMR exome
AF:
0.000291
AC:
13
AN:
44724
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26136
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39700
Gnomad4 SAS exome
AF:
0.00
AC:
0
AN:
86258
Gnomad4 FIN exome
AF:
0.0000375
AC:
2
AN:
53330
Gnomad4 NFE exome
AF:
0.000526
AC:
585
AN:
1112012
Gnomad4 Remaining exome
AF:
0.000281
AC:
17
AN:
60396
Heterozygous variant carriers
0
34
68
103
137
171
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
24
48
72
96
120
<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:
0.000276
AC:
42
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000724
AC:
0.0000723764
AN:
0.0000723764
Gnomad4 AMR
AF:
0.00
AC:
0
AN:
0
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.0000942
AC:
0.0000941974
AN:
0.0000941974
Gnomad4 NFE
AF:
0.000529
AC:
0.000529132
AN:
0.000529132
Gnomad4 OTH
AF:
0.000956
AC:
0.000956023
AN:
0.000956023
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000254
Hom.:
0
Bravo
AF:
0.000238
EpiCase
AF:
0.000436
EpiControl
AF:
0.000474

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial hemophagocytic lymphohistiocytosis 4 Uncertain:1
Jan 28, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant, c.24_26del, results in the deletion of 1 amino acid(s) of the STX11 protein (p.Leu9del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760492745, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with STX11-related conditions. ClinVar contains an entry for this variant (Variation ID: 355597). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Familial hemophagocytic lymphohistiocytosis Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Autoinflammatory syndrome Uncertain:1
Feb 22, 2017
Genome Diagnostics Laboratory, The Hospital for Sick Children
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mutation Taster
=70/30
polymorphism

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.

Other links and lift over

dbSNP: rs760492745; hg19: chr6-144507785; API