11-59755647-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004177.5(STX3):c.30+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 1,592,024 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: STX3 NM_004177.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28

Genes affected

STX3 (HGNC:11438): (syntaxin 3) The gene is a member of the syntaxin family. The encoded protein is targeted to the apical membrane of epithelial cells where it forms clusters and is important in establishing and maintaining polarity necessary for protein trafficking involving vesicle fusion and exocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-59755647-C-T is Benign according to our data. Variant chr11-59755647-C-T is described in ClinVar as [Benign]. Clinvar id is 1601054.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00252 (384/152312) while in subpopulation AFR AF= 0.00863 (359/41588). AF 95% confidence interval is 0.0079. There are 4 homozygotes in gnomad4. There are 179 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX3	NM_004177.5	c.30+12C>T		intron_variant		ENST00000337979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX3	ENST00000337979.9	c.30+12C>T		intron_variant		1	NM_004177.5	A1

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152196 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000614 AC: 138 AN: 224650 Hom.: 1 AF XY: 0.000437 AC XY: 54 AN XY: 123672

Gnomad AFR exome AF: 0.00890

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.000711

GnomAD4 exome AF: 0.000237 AC: 341 AN: 1439712 Hom.: 2 Cov.: 31 AF XY: 0.000186 AC XY: 133 AN XY: 716824

Gnomad4 AFR exome AF: 0.00854

Gnomad4 AMR exome AF: 0.000181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000199

Gnomad4 OTH exome AF: 0.000518

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152312 Hom.: 4 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74480

Gnomad4 AFR AF: 0.00863

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.00291

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

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.9
Dann	Benign	0.94

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: rs199563753; hg19: chr11-59523120;