3-121205916-TC-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001308330.2(STXBP5L):c.878-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: STXBP5L NM_001308330.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0870

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 3-121205916-TC-T is Benign according to our data. Variant chr3-121205916-TC-T is described in ClinVar as [Benign]. Clinvar id is 709374.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5L	NM_001308330.2	c.878-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000471454.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5L	ENST00000471454.6	c.878-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001308330.2	A1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 151790 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.00527 AC: 6270 AN: 1189468 Hom.: 1 Cov.: 19 AF XY: 0.00527 AC XY: 3143 AN XY: 595878

Gnomad4 AFR exome AF: 0.00323

Gnomad4 AMR exome AF: 0.00290

Gnomad4 ASJ exome AF: 0.00476

Gnomad4 EAS exome AF: 0.00442

Gnomad4 SAS exome AF: 0.00618

Gnomad4 FIN exome AF: 0.00292

Gnomad4 NFE exome AF: 0.00551

Gnomad4 OTH exome AF: 0.00496

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000724 AC: 11 AN: 151906 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74270

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000191

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs201466453; hg19: chr3-120924763; COSMIC: COSV56505664;