6-144187466-G-T

Variant names:

• chr6-144187466-G-T
• NM_003764.4:c.839G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003764.4(STX11):​c.839G>T​(p.Cys280Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STX11 NM_003764.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.93

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX11	NM_003764.4	c.839G>T	p.Cys280Phe	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.839G>T	p.Cys280Phe	missense_variant	Exon 2 of 2	1	NM_003764.4	ENSP00000356540.4
STX11	ENST00000698355.1	c.839G>T	p.Cys280Phe	missense_variant	Exon 3 of 3			ENSP00000513678.1
STX11	ENST00000698356.1	c.839G>T	p.Cys280Phe	missense_variant	Exon 4 of 4			ENSP00000513679.1
STX11	ENST00000698357.1	c.839G>T	p.Cys280Phe	missense_variant	Exon 2 of 2			ENSP00000513680.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460084 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.69
Sift	Benign	0.13	T
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.57		Gain of sheet (P = 0.0028);
MVP		0.84
MPC		0.57
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.71
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-144508603;