9-127690698-T-C

Position:

• chr9-127690698-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003165.6(STXBP1):​c.*17-77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 1,451,714 control chromosomes in the GnomAD database, including 1,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (588 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (466 hom.)
• Consequence: STXBP1 NM_003165.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516

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]

MIR3911 (HGNC:38962): (microRNA 3911) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

(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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-127690698-T-C is Benign according to our data. Variant chr9-127690698-T-C is described in ClinVar as [Benign]. Clinvar id is 1241389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP1	NM_001032221.6	c.1703-77T>C		intron_variant		ENST00000373299.5	NP_001027392.1
STXBP1	NM_003165.6	c.*17-77T>C		intron_variant		ENST00000373302.8	NP_003156.1
MIR3911	NR_037473.1	n.98A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP1	ENST00000373299.5	c.1703-77T>C		intron_variant		1	NM_001032221.6	ENSP00000362396	A1
STXBP1	ENST00000373302.8	c.*17-77T>C		intron_variant		1	NM_003165.6	ENSP00000362399	P3
MIR3911	ENST00000577791.1	n.98A>G		non_coding_transcript_exon_variant	1/1
	ENST00000624141.1	n.143A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7161 AN: 151968 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0122 AC: 3042 AN: 250258 Hom.: 229 AF XY: 0.00898 AC XY: 1217 AN XY: 135472

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.00701

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00704

GnomAD4 exome AF: 0.00505 AC: 6563 AN: 1299628 Hom.: 466 Cov.: 20 AF XY: 0.00430 AC XY: 2816 AN XY: 655398

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.00867

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000771

Gnomad4 SAS exome AF: 0.000385

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.000399

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0473 AC: 7190 AN: 152086 Hom.: 588 Cov.: 32 AF XY: 0.0455 AC XY: 3384 AN XY: 74364

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0255 Hom.: 48

Bravo AF: 0.0537

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.47

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: rs57528423; hg19: chr9-130452977;