9-127690513-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003165.6(STXBP1):c.*17-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 539,606 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (80 hom., cov: 32)
  • Exomes 𝑓: 0.032 (236 hom.)
• Consequence: STXBP1 NM_003165.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980

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]

(HGNC:):

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-127690513-G-A is Benign according to our data. Variant chr9-127690513-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0294 (4476/152306) while in subpopulation NFE AF= 0.0397 (2698/68032). AF 95% confidence interval is 0.0384. There are 80 homozygotes in gnomad4. There are 2166 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP1	NM_001032221.6	c.1703-262G>A		intron_variant		ENST00000373299.5
STXBP1	NM_003165.6	c.*17-262G>A		intron_variant		ENST00000373302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP1	ENST00000373299.5	c.1703-262G>A		intron_variant		1	NM_001032221.6	A1
STXBP1	ENST00000373302.8	c.*17-262G>A		intron_variant		1	NM_003165.6	P3
	ENST00000624141.1	n.328C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4476 AN: 152188 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.0317 AC: 12290 AN: 387300 Hom.: 236 Cov.: 0 AF XY: 0.0318 AC XY: 6531 AN XY: 205170

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.0277

Gnomad4 FIN exome AF: 0.0293

Gnomad4 NFE exome AF: 0.0379

Gnomad4 OTH exome AF: 0.0294

GnomAD4 genome AF: 0.0294 AC: 4476 AN: 152306 Hom.: 80 Cov.: 32 AF XY: 0.0291 AC XY: 2166 AN XY: 74470

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0364 Hom.: 17

Bravo AF: 0.0285

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.33

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

Other links and lift over

dbSNP: rs72752811; hg19: chr9-130452792;