11-59755647-C-T

Variant names:

• chr11-59755647-C-T
• rs199563753
• NM_004177.5:c.30+12C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

STX3 Gene-Disease associations (from GenCC):

• diarrhea 12, with microvillus atrophy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• retinal dystrophy and microvillus inclusion disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• microvillus inclusion disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004177.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX3	NM_004177.5	MANE Select	c.30+12C>T		intron	N/A	NP_004168.1	Q13277-1
	STX3	NM_001440522.1		c.30+12C>T		intron	N/A	NP_001427451.1
	STX3	NM_001440523.1		c.30+12C>T		intron	N/A	NP_001427452.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX3	ENST00000337979.9	TSL:1 MANE Select	c.30+12C>T		intron	N/A	ENSP00000338562.4	Q13277-1
	STX3	ENST00000530221.2	TSL:5	c.30+12C>T		intron	N/A	ENSP00000434836.2
	STX3	ENST00000887353.1		c.30+12C>T		intron	N/A	ENSP00000557412.1

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

GnomAD2 exomes AF: 0.000614 AC: 138 AN: 224650 AF XY: 0.000437

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 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

African (AFR) AF: 0.00854 AC: 278 AN: 32546

American (AMR) AF: 0.000181 AC: 8 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38232

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1107176

Other (OTH) AF: 0.000518 AC: 31 AN: 59816

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

African (AFR) AF: 0.00863 AC: 359 AN: 41588

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.00291

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.9
DANN	Benign	0.94
PhyloP100		-2.3
PromoterAI		-0.094	Neutral
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: rs199563753; hg19: chr11-59523120;