dbSNP rs766292057: STX3:p.Arg4Ser (chr11-59755615-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004177.5(STX3):c.10C>A(p.Arg4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STX3
NM_004177.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

Publications

0 publications found

Variant links:

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

STX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33689016).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX3	NM_004177.5	MANE Select	c.10C>A	p.Arg4Ser	missense	Exon 1 of 11	NP_004168.1	Q13277-1
STX3	NM_001440522.1		c.10C>A	p.Arg4Ser	missense	Exon 1 of 11	NP_001427451.1
STX3	NM_001440523.1		c.10C>A	p.Arg4Ser	missense	Exon 1 of 11	NP_001427452.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX3	ENST00000337979.9	TSL:1 MANE Select	c.10C>A	p.Arg4Ser	missense	Exon 1 of 11	ENSP00000338562.4	Q13277-1
STX3	ENST00000530221.2	TSL:5	c.10C>A	p.Arg4Ser	missense	Exon 1 of 11	ENSP00000434836.2
STX3	ENST00000887353.1		c.10C>A	p.Arg4Ser	missense	Exon 2 of 12	ENSP00000557412.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718230

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32714

American (AMR)

AF:

0.00

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25918

East Asian (EAS)

AF:

0.00

AC:

AN:

38558

South Asian (SAS)

AF:

0.00

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108536

Other (OTH)

AF:

0.00

AC:

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PhyloP100

0.52

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.19

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.81

Vest4

0.40

MutPred

0.54

Loss of MoRF binding (P = 0.0267)

MVP

0.61

MPC

0.19

ClinPred

0.78

GERP RS

2.7

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.81

Mutation Taster

=74/26

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over