rs542557411

Variant names:

• chr19-7646285-C-A
• NM_006949.4:c.1393C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7646285-C-A
• chr19-7646285-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006949.4(STXBP2):​c.1393C>A​(p.Arg465Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: STXBP2 NM_006949.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16

Genes affected

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

ENSG00000268400 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4	c.1393C>A	p.Arg465Ser	missense_variant	Exon 16 of 19	ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10	c.1393C>A	p.Arg465Ser	missense_variant	Exon 16 of 19	1	NM_006949.4	ENSP00000221283.4
ENSG00000268400	ENST00000698368.1	n.*1496C>A		non_coding_transcript_exon_variant	Exon 18 of 20			ENSP00000513686.1
ENSG00000268400	ENST00000698368.1	n.*1496C>A		3_prime_UTR_variant	Exon 18 of 20			ENSP00000513686.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459028 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.0074
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.3	.;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.75
MutPred		0.44		.;Gain of phosphorylation at R465 (P = 0.0058);.;
MVP		0.84
MPC		0.46
ClinPred		0.95	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-7711171;