9-127690612-C-T

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.*17-163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 773,436 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (13 hom.)
• Consequence: STXBP1 NM_003165.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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=-0.86).
• BP6: Variant 9-127690612-C-T is Benign according to our data. Variant chr9-127690612-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 677438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1773/152160) while in subpopulation AFR AF= 0.0398 (1650/41480). AF 95% confidence interval is 0.0382. There are 41 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1769 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP1	NM_001032221.6	c.1703-163C>T		intron_variant		ENST00000373299.5
STXBP1	NM_003165.6	c.*17-163C>T		intron_variant		ENST00000373302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP1	ENST00000373299.5	c.1703-163C>T		intron_variant		1	NM_001032221.6	A1
STXBP1	ENST00000373302.8	c.*17-163C>T		intron_variant		1	NM_003165.6	P3
	ENST00000624141.1	n.229G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1769 AN: 152042 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00178 AC: 1104 AN: 621276 Hom.: 13 Cov.: 7 AF XY: 0.00138 AC XY: 464 AN XY: 335422

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.00337

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000282

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.0000197

Gnomad4 NFE exome AF: 0.000302

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.0117 AC: 1773 AN: 152160 Hom.: 41 Cov.: 32 AF XY: 0.0114 AC XY: 846 AN XY: 74382

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00950 Hom.: 1

Bravo AF: 0.0130

Asia WGS AF: 0.00346 AC: 12 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

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.7
Dann	Benign	0.63

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: rs116088144; hg19: chr9-130452891;