Variant 9-127612428-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_003165.6(STXBP1):c.25G>A(p.Val9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STXBP1
NM_003165.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00300

Variant links:

Genes affected

STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

STXBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STXBP1. . Gene score misZ 4.263 (greater than the threshold 3.09). Trascript score misZ 5.8329 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant non-syndromic intellectual disability, Dravet syndrome, undetermined early-onset epileptic encephalopathy, autism spectrum disorder, developmental and epileptic encephalopathy, West syndrome, atypical Rett syndrome, developmental and epileptic encephalopathy, 4.

BP4

Computational evidence support a benign effect (MetaRNN=0.20109111).

BP6

Variant 9-127612428-G-A is Benign according to our data. Variant chr9-127612428-G-A is described in ClinVar as [Benign]. Clinvar id is 461292.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP1	NM_003165.6 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	1/20	ENST00000373302.8	NP_003156.1
STXBP1	NM_001032221.6 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	1/19	ENST00000373299.5	NP_001027392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373302.8 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	1/20	1	NM_003165.6	ENSP00000362399	P3	P61764-2
STXBP1	ENST00000373299.5 linkuse as main transcript	c.25G>A	p.Val9Ile	missense_variant	1/19	1	NM_001032221.6	ENSP00000362396	A1	P61764-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

229032

Hom.:

AF XY:

0.00000795

AC XY:

AN XY:

125798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445708

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000458

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0021

.;T;.;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;D;D;D;.

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.030

N;.;.;N;.

MutationTaster

Benign

0.91

N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.14

N;.;.;N;.

REVEL

Benign

0.20

Sift

Benign

0.50

T;.;.;T;.

Sift4G

Benign

0.65

T;.;.;T;.

Polyphen

0.0010

B;.;.;B;.

Vest4

0.17

MutPred

0.42

Loss of ubiquitination at K7 (P = 0.0811);Loss of ubiquitination at K7 (P = 0.0811);Loss of ubiquitination at K7 (P = 0.0811);Loss of ubiquitination at K7 (P = 0.0811);Loss of ubiquitination at K7 (P = 0.0811);

MVP

0.20

MPC

1.0

ClinPred

0.12

GERP RS

2.7

Varity_R

0.055

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over