NM_001308330.2:c.2177-12625T>C

Variant names:

• chr3-121366091-T-C
• rs35827958
• NM_001308330.2:c.2177-12625T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308330.2(STXBP5L):​c.2177-12625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 152,108 control chromosomes in the GnomAD database, including 125 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 0.034 (125 hom., cov: 32)
• Consequence: STXBP5L NM_001308330.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5L	NM_001308330.2	c.2177-12625T>C		intron_variant	Intron 20 of 26	ENST00000471454.6	NP_001295259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP5L	ENST00000471454.6	c.2177-12625T>C		intron_variant	Intron 20 of 26	2	NM_001308330.2	ENSP00000420019.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5141 AN: 151990 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0338 AC: 5136 AN: 152108 Hom.: 125 Cov.: 32 AF XY: 0.0333 AC XY: 2474 AN XY: 74364

African (AFR) AF: 0.0152 AC: 630 AN: 41574

American (AMR) AF: 0.0342 AC: 523 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 161 AN: 3466

East Asian (EAS) AF: 0.0731 AC: 379 AN: 5188

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4828

European-Finnish (FIN) AF: 0.0248 AC: 263 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0404 AC: 2744 AN: 67840

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0438 Hom.: 31

Bravo AF: 0.0329

Asia WGS AF: 0.0740 AC: 257 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.49
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: rs35827958; hg19: chr3-121084938;