NM_004177.5:c.122A>G

Variant names:

• chr11-59787044-A-G
• rs797045154
• NM_004177.5:c.122A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004177.5(STX3):​c.122A>G​(p.Glu41Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX3 NM_004177.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.43
• Publications: 3 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.122A>G	p.Glu41Gly	missense	Exon 3 of 11	NP_004168.1	Q13277-1
	STX3	NM_001440522.1		c.122A>G	p.Glu41Gly	missense	Exon 3 of 11	NP_001427451.1
	STX3	NM_001440523.1		c.122A>G	p.Glu41Gly	missense	Exon 3 of 11	NP_001427452.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX3	ENST00000337979.9	TSL:1 MANE Select	c.122A>G	p.Glu41Gly	missense	Exon 3 of 11	ENSP00000338562.4	Q13277-1
	STX3	ENST00000530221.2	TSL:5	c.122A>G	p.Glu41Gly	missense	Exon 3 of 11	ENSP00000434836.2
	STX3	ENST00000887353.1		c.122A>G	p.Glu41Gly	missense	Exon 4 of 12	ENSP00000557412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.21
Sift	Benign	0.049	D
Sift4G	Uncertain	0.051	T
Polyphen		0.98	D
Vest4		0.50
MutPred		0.50		Loss of stability (P = 0.0518)
MVP		0.36
MPC		0.22
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		-0.030	Neutral
Varity_R		0.34
gMVP		0.34
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs797045154; hg19: chr11-59554517; COSMIC: COSV100276312; COSMIC: COSV100276312;