Variant 16-31357272-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000887.5(ITGAX):c.338A>G(p.His113Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ITGAX
NM_000887.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

ITGAX (HGNC:6152): (integrin subunit alpha X) This gene encodes the integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap the properties of the alpha M beta 2 integrin in the adherence of neutrophils and monocytes to stimulated endothelium cells, and in the phagocytosis of complement coated particles. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ITGAX links:

ITGAX (HGNC:):

ITGAX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAX	NM_000887.5 linkuse as main transcript	c.338A>G	p.His113Arg	missense_variant	5/30	ENST00000268296.9	NP_000878.2	P20702

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGAX	ENST00000268296.9 linkuse as main transcript	c.338A>G	p.His113Arg	missense_variant	5/30	1	NM_000887.5	ENSP00000268296.5	P20702
ITGAX	ENST00000562522.2 linkuse as main transcript	c.338A>G	p.His113Arg	missense_variant	5/31	1		ENSP00000454623.1	H3BN02
ITGAX	ENST00000567409.1 linkuse as main transcript	n.556A>G		non_coding_transcript_exon_variant	4/4	1
ITGAX	ENST00000562918.5 linkuse as main transcript	c.319-62A>G		intron_variant		2		ENSP00000483860.1	A0A087X131

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454630

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.338A>G (p.H113R) alteration is located in exon 5 (coding exon 5) of the ITGAX gene. This alteration results from a A to G substitution at nucleotide position 338, causing the histidine (H) at amino acid position 113 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Uncertain

0.54

D;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.50

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Uncertain

0.33

Sift

Benign

0.20

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.74

P;.

Vest4

0.53

MutPred

0.36

Gain of phosphorylation at T111 (P = 0.0998);Gain of phosphorylation at T111 (P = 0.0998);

MVP

0.77

MPC

0.31

ClinPred

0.30

GERP RS

5.0

Varity_R

0.47

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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