16-31363214-C-T

Variant names:

• chr16-31363214-C-T
• rs2230429
• NM_000887.5:c.1550C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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 Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITGAX NM_000887.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 43 publications found

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]

ACMG classification

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=0.39727753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000887.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	NM_000887.5	MANE Select	c.1550C>T	p.Pro517Leu	missense	Exon 14 of 30	NP_000878.2
	ITGAX	NM_001286375.2		c.1550C>T	p.Pro517Leu	missense	Exon 14 of 31	NP_001273304.1	H3BN02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	ENST00000268296.9	TSL:1 MANE Select	c.1550C>T	p.Pro517Leu	missense	Exon 14 of 30	ENSP00000268296.5	P20702
	ITGAX	ENST00000562522.2	TSL:1	c.1550C>T	p.Pro517Leu	missense	Exon 14 of 31	ENSP00000454623.1	H3BN02
	ITGAX	ENST00000958326.1		c.1505C>T	p.Pro502Leu	missense	Exon 14 of 30	ENSP00000628385.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Benign	0.18
Sift	Benign	0.039	D
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.43		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

Other links and lift over

dbSNP: rs2230429; hg19: chr16-31374535;