rs2230429

Positions:

• chr16-31363214-C-A
• chr16-31363214-C-G
• chr16-31363214-C-T

Variant summary

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

The NM_000887.5(ITGAX):​c.1550C>A​(p.Pro517His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• 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]

ACMG classification

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	UniProt
ITGAX	NM_000887.5	c.1550C>A	p.Pro517His	missense_variant	14/30	ENST00000268296.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAX	ENST00000268296.9	c.1550C>A	p.Pro517His	missense_variant	14/30	1	NM_000887.5	P4
ITGAX	ENST00000562522.2	c.1550C>A	p.Pro517His	missense_variant	14/31	1		A2
ITGAX	ENST00000571644.1	n.1571C>A		non_coding_transcript_exon_variant	7/22	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461016 Hom.: 0 Cov.: 53 AF XY: 0.00000138 AC XY: 1 AN XY: 726834

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.7	H;.
MutationTaster	Benign	0.95	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-8.2	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.086	T;T
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.33		Gain of methylation at R520 (P = 0.0851);Gain of methylation at R520 (P = 0.0851);
MVP		0.78
MPC		0.82
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.70
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;