rs483352901

Positions:

• chr6-144186995-CAGTGGCGC-CTGG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_003764.4(STX11):​c.369_376delinsTGG​(p.Val124GlyfsTer60) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX11 NM_003764.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.58

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.573 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-144186996-AGTGGCGC-TGG is Pathogenic according to our data. Variant chr6-144186996-AGTGGCGC-TGG is described in ClinVar as [Pathogenic]. Clinvar id is 5263.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX11	NM_003764.4	c.369_376delinsTGG	p.Val124GlyfsTer60	frameshift_variant	2/2	ENST00000367568.5	NP_003755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX11	ENST00000367568.5	c.369_376delinsTGG	p.Val124GlyfsTer60	frameshift_variant	2/2	1	NM_003764.4	ENSP00000356540	P1
STX11	ENST00000698355.1	c.369_376delinsTGG	p.Val124GlyfsTer60	frameshift_variant	3/3			ENSP00000513678	P1
STX11	ENST00000698356.1	c.369_376delinsTGG	p.Val124GlyfsTer60	frameshift_variant	4/4			ENSP00000513679	P1
STX11	ENST00000698357.1	c.369_376delinsTGG	p.Val124GlyfsTer60	frameshift_variant	2/2			ENSP00000513680	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Familial hemophagocytic lymphohistiocytosis 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2006

- -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Clinical Genetics and Genomics, Karolinska University Hospital

Oct 02, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs483352901; hg19: chr6-144508133;