NM_032208.3:c.77C>T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032208.3(ANTXR1):c.77C>T(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,571,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ANTXR1
NM_032208.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.16

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09209213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR1	NM_032208.3 link	c.77C>T	p.Ala26Val	missense_variant	Exon 1 of 18	ENST00000303714.9	NP_115584.1	Q9H6X2-1Q53FL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9 link	c.77C>T	p.Ala26Val	missense_variant	Exon 1 of 18	1	NM_032208.3	ENSP00000301945.4		Q9H6X2-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000225

AC:

AN:

178134

Hom.:

AF XY:

0.0000212

AC XY:

AN XY:

94522

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000143

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000345

AC:

AN:

1418796

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

701200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000376

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000347

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77C>T (p.A26V) alteration is located in exon 1 (coding exon 1) of the ANTXR1 gene. This alteration results from a C to T substitution at nucleotide position 77, causing the alanine (A) at amino acid position 26 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Aug 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1907395). This variant has not been reported in the literature in individuals affected with ANTXR1-related conditions. This variant is present in population databases (rs763539838, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 26 of the ANTXR1 protein (p.Ala26Val). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.82

T;T;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.035

B;B;B

Vest4

0.20

MutPred

0.60

Loss of disorder (P = 0.0988);Loss of disorder (P = 0.0988);Loss of disorder (P = 0.0988);

MVP

0.35

MPC

0.95

ClinPred

0.11

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over