NM_003165.6:c.*17-102T>C

Variant names:

• chr9-127690673-T-C
• rs750631170
• NM_003165.6:c.*17-102T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_003165.6(STXBP1):​c.*17-102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,239,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: STXBP1 NM_003165.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-127690673-T-C is Benign according to our data. Variant chr9-127690673-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1253857.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003165.6. 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.*17-102T>C		intron	N/A	NP_003156.1	P61764-2
	STXBP1	NM_001032221.6	MANE Select	c.1703-102T>C		intron	N/A	NP_001027392.1	P61764-1
	STXBP1	NM_001374306.2		c.1694-102T>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.*17-102T>C		intron	N/A	ENSP00000362399.3	P61764-2
	STXBP1	ENST00000373299.5	TSL:1 MANE Select	c.1703-102T>C		intron	N/A	ENSP00000362396.2	P61764-1
	PTRH1	ENST00000641641.1		c.*77A>G		3_prime_UTR	Exon 2 of 2	ENSP00000492921.1	A0A286YER0

Frequencies

GnomAD3 genomes AF: 0.000225 AC: 34 AN: 151382 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000369

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000173 AC: 43 AN: 249002 AF XY: 0.000170

Gnomad AFR exome AF: 0.0000633

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000348

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000264 AC: 287 AN: 1088176 Hom.: 0 Cov.: 15 AF XY: 0.000265 AC XY: 148 AN XY: 558284

African (AFR) AF: 0.0000385 AC: 1 AN: 25984

American (AMR) AF: 0.0000679 AC: 3 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23836

East Asian (EAS) AF: 0.00 AC: 0 AN: 37876

South Asian (SAS) AF: 0.00 AC: 0 AN: 78544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5004

European-Non Finnish (NFE) AF: 0.000360 AC: 278 AN: 771790

Other (OTH) AF: 0.000104 AC: 5 AN: 48128

GnomAD4 genome AF: 0.000225 AC: 34 AN: 151382 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 73924

African (AFR) AF: 0.000122 AC: 5 AN: 41114

American (AMR) AF: 0.000197 AC: 3 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000369 AC: 25 AN: 67792

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.0000727 Hom.: 0

Bravo AF: 0.000212

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	-0.58
CADD	Benign	4.1
DANN	Benign	0.65
PhyloP100		0.064
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: rs750631170; hg19: chr9-130452952;