9-127690612-C-T

Variant names:

• chr9-127690612-C-T
• rs116088144
• NM_003165.6:c.*17-163C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001032221.6(STXBP1):​c.1703-163C>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_001032221.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114
• Publications: 0 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]

ENSG00000279571 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AD,AR gene

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.*17-163C>T		intron	N/A	NP_003156.1	P61764-2
	STXBP1	NM_001032221.6	MANE Select	c.1703-163C>T		intron	N/A	NP_001027392.1	P61764-1
	STXBP1	NM_001374306.2		c.1694-163C>T		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.*17-163C>T		intron	N/A	ENSP00000362399.3	P61764-2
	STXBP1	ENST00000373299.5	TSL:1 MANE Select	c.1703-163C>T		intron	N/A	ENSP00000362396.2	P61764-1
	PTRH1	ENST00000641641.1		c.*138G>A		3_prime_UTR	Exon 2 of 2	ENSP00000492921.1	A0A286YER0

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

African (AFR) AF: 0.0410 AC: 706 AN: 17236

American (AMR) AF: 0.00337 AC: 137 AN: 40626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19254

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35488

South Asian (SAS) AF: 0.000244 AC: 16 AN: 65570

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50732

Middle Eastern (MID) AF: 0.00569 AC: 17 AN: 2990

European-Non Finnish (NFE) AF: 0.000302 AC: 108 AN: 357084

Other (OTH) AF: 0.00365 AC: 118 AN: 32296

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

African (AFR) AF: 0.0398 AC: 1650 AN: 41480

American (AMR) AF: 0.00504 AC: 77 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68002

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00714 Hom.: 1

Bravo AF: 0.0130

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

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: rs116088144; hg19: chr9-130452891;