Genetic Variant ANTXR1:p.Leu45Met (chr2-69013632-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032208.3(ANTXR1):c.133C>A(p.Leu45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L45V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANTXR1
NM_032208.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

Publications

0 publications found

Variant links:

Genes affected

ANTXR1 (HGNC:21014): (ANTXR cell adhesion molecule 1) This gene encodes a type I transmembrane protein and is a tumor-specific endothelial marker that has been implicated in colorectal cancer. The encoded protein has been shown to also be a docking protein or receptor for Bacillus anthracis toxin, the causative agent of the disease, anthrax. The binding of the protective antigen (PA) component, of the tripartite anthrax toxin, to this receptor protein mediates delivery of toxin components to the cytosol of cells. Once inside the cell, the other two components of anthrax toxin, edema factor (EF) and lethal factor (LF) disrupt normal cellular processes. Three alternatively spliced variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ANTXR1 Gene-Disease associations (from GenCC):

GAPO syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
capillary infantile hemangioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANTXR1 links:

ENSG00000300948 (HGNC:):

ENSG00000300948 links:

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ACMG classification

Classification was made for transcript

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_032208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANTXR1	NM_032208.3	MANE Select	c.133C>A	p.Leu45Met	missense	Exon 1 of 18	NP_115584.1	Q9H6X2-1
ANTXR1	NM_053034.2		c.133C>A	p.Leu45Met	missense	Exon 1 of 15	NP_444262.1	Q9H6X2-2
ANTXR1	NM_001410840.1		c.133C>A	p.Leu45Met	missense	Exon 1 of 13	NP_001397769.1	H0YC24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.133C>A	p.Leu45Met	missense	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
ANTXR1	ENST00000409349.7	TSL:1	c.133C>A	p.Leu45Met	missense	Exon 1 of 15	ENSP00000386494.3	Q9H6X2-2
ANTXR1	ENST00000409829.7	TSL:1	c.133C>A	p.Leu45Met	missense	Exon 1 of 13	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691370

African (AFR)

AF:

0.00

AC:

AN:

31914

American (AMR)

AF:

0.00

AC:

AN:

35778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

36306

South Asian (SAS)

AF:

0.00

AC:

AN:

79392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079818

Other (OTH)

AF:

0.00

AC:

AN:

58082

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

2.9

PhyloP100

2.2

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.64

Sift

Benign

0.062

Sift4G

Uncertain

0.046

Polyphen

0.88

Vest4

0.67

MutPred

0.53

Gain of sheet (P = 0.0827)

MVP

0.81

MPC

2.0

ClinPred

0.98

GERP RS

5.1

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.39

gMVP

0.71

Mutation Taster

=63/37

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over