6-144187426-G-T

Variant names:

• chr6-144187426-G-T
• rs45574234
• NM_003764.4:c.799G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003764.4(STX11):​c.799G>T​(p.Val267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V267M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX11 NM_003764.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen
• hereditary hemophagocytic lymphohistiocytosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1545074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX11	NM_003764.4	c.799G>T	p.Val267Leu	missense_variant	Exon 2 of 2	ENST00000367568.5	NP_003755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX11	ENST00000367568.5	c.799G>T	p.Val267Leu	missense_variant	Exon 2 of 2	1	NM_003764.4	ENSP00000356540.4
STX11	ENST00000698355.1	c.799G>T	p.Val267Leu	missense_variant	Exon 3 of 3			ENSP00000513678.1
STX11	ENST00000698356.1	c.799G>T	p.Val267Leu	missense_variant	Exon 4 of 4			ENSP00000513679.1
STX11	ENST00000698357.1	c.799G>T	p.Val267Leu	missense_variant	Exon 2 of 2			ENSP00000513680.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.099
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.035	B
Vest4		0.041
MutPred		0.48		Loss of methylation at K272 (P = 0.0863);
MVP		0.52
MPC		0.39
ClinPred		0.55	D
GERP RS		2.9
Varity_R		0.15
gMVP		0.31
Mutation Taster		=90/10	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

Other links and lift over

dbSNP: rs45574234; hg19: chr6-144508563;