16-31363214-C-T

Position:

• chr16-31363214-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000887.5(ITGAX):​c.1550C>T​(p.Pro517Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P517R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITGAX NM_000887.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39727753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.1550C>T	p.Pro517Leu	missense_variant	14/30	ENST00000268296.9	NP_000878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.1550C>T	p.Pro517Leu	missense_variant	14/30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.1550C>T	p.Pro517Leu	missense_variant	14/31	1		ENSP00000454623.1
ITGAX	ENST00000571644.1	n.1571C>T		non_coding_transcript_exon_variant	7/22	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.7	D;D
REVEL	Benign	0.18
Sift	Benign	0.039	D;D
Sift4G	Benign	0.22	T;T
Polyphen		1.0	D;.
Vest4		0.44
MutPred		0.43		Gain of MoRF binding (P = 0.1056);Gain of MoRF binding (P = 0.1056);
MVP		0.69
MPC		0.77
ClinPred		0.94	D
GERP RS		4.0
Varity_R		0.41
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs2230429; hg19: chr16-31374535;