rs199563753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-59755647-C-A
• chr11-59755647-C-G
• chr11-59755647-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004177.5(STX3):​c.30+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,439,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: STX3 NM_004177.5 intron
• Clinical Significance: Likely 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-59755647-C-A is Benign according to our data. Variant chr11-59755647-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1545232.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A		intron	N/A	NP_004168.1	Q13277-1
	STX3	NM_001440522.1		c.30+12C>A		intron	N/A	NP_001427451.1
	STX3	NM_001440523.1		c.30+12C>A		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>A		intron	N/A	ENSP00000338562.4	Q13277-1
	STX3	ENST00000530221.2	TSL:5	c.30+12C>A		intron	N/A	ENSP00000434836.2
	STX3	ENST00000887353.1		c.30+12C>A		intron	N/A	ENSP00000557412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1439714 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716824

African (AFR) AF: 0.00 AC: 0 AN: 32548

American (AMR) AF: 0.00 AC: 0 AN: 44162

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 38232

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1107176

Other (OTH) AF: 0.0000502 AC: 3 AN: 59816

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.72
CADD	Benign	2.2
DANN	Benign	0.86
PhyloP100		-2.3
PromoterAI		-0.080	Neutral

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;