9-127690698-T-C

Variant names:

• chr9-127690698-T-C
• rs57528423
• NM_003165.6:c.*17-77T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001032221.6(STXBP1):​c.1703-77T>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_001032221.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516
• Publications: 3 publications found

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]

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

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]

ENSG00000279571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032221.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP1	NM_003165.6	MANE Plus Clinical	c.*17-77T>C		intron	N/A	NP_003156.1	P61764-2
	STXBP1	NM_001032221.6	MANE Select	c.1703-77T>C		intron	N/A	NP_001027392.1	P61764-1
	STXBP1	NM_001374306.2		c.1694-77T>C		intron	N/A	NP_001361235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP1	ENST00000373302.8	TSL:1 MANE Plus Clinical	c.*17-77T>C		intron	N/A	ENSP00000362399.3	P61764-2
	STXBP1	ENST00000373299.5	TSL:1 MANE Select	c.1703-77T>C		intron	N/A	ENSP00000362396.2	P61764-1
	PTRH1	ENST00000641641.1		c.*52A>G		3_prime_UTR	Exon 2 of 2	ENSP00000492921.1	A0A286YER0

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

GnomAD2 exomes AF: 0.0122 AC: 3042 AN: 250258 AF XY: 0.00898

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 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

African (AFR) AF: 0.171 AC: 5143 AN: 30064

American (AMR) AF: 0.00867 AC: 386 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.0000771 AC: 3 AN: 38890

South Asian (SAS) AF: 0.000385 AC: 32 AN: 83042

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53184

Middle Eastern (MID) AF: 0.00772 AC: 42 AN: 5440

European-Non Finnish (NFE) AF: 0.000399 AC: 385 AN: 964332

Other (OTH) AF: 0.0104 AC: 570 AN: 55072

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

African (AFR) AF: 0.165 AC: 6823 AN: 41400

American (AMR) AF: 0.0171 AC: 261 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68004

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0287 Hom.: 55

Bravo AF: 0.0537

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.47
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57528423; hg19: chr9-130452977;