rs78010345

Variant names:

• chr19-7642450-C-G
• NM_006949.4:c.816C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-7642450-C-G
• chr19-7642450-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006949.4(STXBP2):​c.816C>G​(p.Ser272Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 0.0000021 (0 hom.)
• Consequence: STXBP2 NM_006949.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18841699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4	c.816C>G	p.Ser272Arg	missense_variant	Exon 10 of 19	ENST00000221283.10	NP_008880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10	c.816C>G	p.Ser272Arg	missense_variant	Exon 10 of 19	1	NM_006949.4	ENSP00000221283.4
ENSG00000268400	ENST00000698368.1	n.*919C>G		non_coding_transcript_exon_variant	Exon 12 of 20			ENSP00000513686.1
ENSG00000268400	ENST00000698368.1	n.*919C>G		3_prime_UTR_variant	Exon 12 of 20			ENSP00000513686.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461674 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727168

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: 0.00000270

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	0.71
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.1
DANN	Benign	0.94
DEOGEN2	Benign	0.33	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.080	T;T;T
Sift4G	Benign	0.081	T;T;T
Polyphen		0.46, 0.83	.;P;P
Vest4		0.38
MutPred		0.43		.;Loss of phosphorylation at S272 (P = 0.0349);.;
MVP		0.37
MPC		0.85
ClinPred		0.71	D
GERP RS		-9.4
Varity_R		0.50
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-7707336; COSMIC: COSV55404494; COSMIC: COSV55404494;