3-121316854-G-C

Variant names:

• chr3-121316854-G-C
• rs9332451
• NM_001308330.2:c.2111-1621G>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.2111-1621G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,838 control chromosomes in the GnomAD database, including 18,639 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 0.49 (18639 hom., cov: 31)
• Consequence: STXBP5L NM_001308330.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308330.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5L	NM_001308330.2	MANE Select	c.2111-1621G>C		intron	N/A	NP_001295259.1
	STXBP5L	NM_001348343.2		c.2183-1621G>C		intron	N/A	NP_001335272.1
	STXBP5L	NM_014980.3		c.2183-1621G>C		intron	N/A	NP_055795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5L	ENST00000471454.6	TSL:2 MANE Select	c.2111-1621G>C		intron	N/A	ENSP00000420019.1
	STXBP5L	ENST00000273666.10	TSL:1	c.2183-1621G>C		intron	N/A	ENSP00000273666.6
	STXBP5L	ENST00000707001.1		c.2183-1621G>C		intron	N/A	ENSP00000516710.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74292 AN: 151722 Hom.: 18637 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.489 AC: 74321 AN: 151838 Hom.: 18639 Cov.: 31 AF XY: 0.493 AC XY: 36556 AN XY: 74216

African (AFR) AF: 0.425 AC: 17602 AN: 41382

American (AMR) AF: 0.402 AC: 6138 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1680 AN: 3464

East Asian (EAS) AF: 0.730 AC: 3770 AN: 5162

South Asian (SAS) AF: 0.616 AC: 2971 AN: 4826

European-Finnish (FIN) AF: 0.509 AC: 5360 AN: 10532

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.516 AC: 35031 AN: 67912

Other (OTH) AF: 0.502 AC: 1058 AN: 2108

Alfa AF: 0.344 Hom.: 856

Bravo AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.31
PhyloP100		-0.20
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: rs9332451; hg19: chr3-121035701;