3-121365620-C-T

Variant names:

• chr3-121365620-C-T
• rs11707293
• NM_001308330.2:c.2177-13096C>T

Variant summary

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

The NM_001308330.2(STXBP5L):​c.2177-13096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,100 control chromosomes in the GnomAD database, including 18,151 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 0.48 (18151 hom., cov: 30)
• Consequence: STXBP5L NM_001308330.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5L	NM_001308330.2	c.2177-13096C>T		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.2177-13096C>T		intron_variant	Intron 20 of 26	2	NM_001308330.2	ENSP00000420019.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 72991 AN: 150982 Hom.: 18149 Cov.: 30

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.483 AC: 73022 AN: 151100 Hom.: 18151 Cov.: 30 AF XY: 0.487 AC XY: 35905 AN XY: 73784

African (AFR) AF: 0.399 AC: 16475 AN: 41274

American (AMR) AF: 0.400 AC: 6086 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1728 AN: 3458

East Asian (EAS) AF: 0.712 AC: 3673 AN: 5160

South Asian (SAS) AF: 0.621 AC: 2979 AN: 4800

European-Finnish (FIN) AF: 0.512 AC: 5312 AN: 10380

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35004 AN: 67516

Other (OTH) AF: 0.498 AC: 1048 AN: 2104

Alfa AF: 0.503 Hom.: 16961

Bravo AF: 0.470

Asia WGS AF: 0.666 AC: 2305 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		0.055
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: rs11707293; hg19: chr3-121084467;