rs13086038

Positions:

• chr3-121352649-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308330.2(STXBP5L):​c.2177-26067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 152,128 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (201 hom., cov: 32)
• Consequence: STXBP5L NM_001308330.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

Genes affected

STXBP5L (HGNC:30757): (syntaxin binding protein 5L) The protein encoded by this gene is similar to syntaxin-binding protein 5 and contains ten N-terminal WD40 repeats, four variable region WD40 repeats, and a C-terminal R-SNARE domain. Studies of the orthologous proteins in mouse and rat have shown that the encoded protein may inhibit exocytosis in neurosecretory cells, and may negatively regulate the secretion of insulin. A missense variant in this gene is likely the cause of an infantile-onset neurodegenerative disorder diagnosed in two siblings of consanguineous parents. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP5L	NM_001308330.2	c.2177-26067T>C		intron_variant		ENST00000471454.6	NP_001295259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP5L	ENST00000471454.6	c.2177-26067T>C		intron_variant		2	NM_001308330.2	ENSP00000420019	A1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6960 AN: 152012 Hom.: 201 Cov.: 32

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.0486

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0457 AC: 6958 AN: 152128 Hom.: 201 Cov.: 32 AF XY: 0.0458 AC XY: 3406 AN XY: 74378

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0414

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0410

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0503 Hom.: 35

Bravo AF: 0.0462

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.65

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: rs13086038; hg19: chr3-121071496;