chr16-31356669-C-G

Variant names:

• chr16-31356669-C-G
• rs375890125
• NM_000887.5:c.188C>G

Variant summary

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

The NM_000887.5(ITGAX):​c.188C>G​(p.Thr63Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGAX NM_000887.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.309843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.188C>G	p.Thr63Arg	missense_variant	Exon 3 of 30	ENST00000268296.9	NP_000878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.188C>G	p.Thr63Arg	missense_variant	Exon 3 of 30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.188C>G	p.Thr63Arg	missense_variant	Exon 3 of 31	1		ENSP00000454623.1
ITGAX	ENST00000567409.1	n.255C>G		non_coding_transcript_exon_variant	Exon 3 of 4	1
ITGAX	ENST00000562918.5	c.188C>G	p.Thr63Arg	missense_variant	Exon 3 of 5	2		ENSP00000483860.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Uncertain	0.53	D;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.0	D;.;D
REVEL	Uncertain	0.32
Sift	Benign	0.084	T;.;T
Sift4G	Benign	0.10	T;D;T
Polyphen		1.0	D;.;.
Vest4		0.41
MutPred		0.48		Gain of methylation at T63 (P = 0.0296);Gain of methylation at T63 (P = 0.0296);Gain of methylation at T63 (P = 0.0296);
MVP		0.68
MPC		0.79
ClinPred		0.65	D
GERP RS		3.4
Varity_R		0.42
gMVP		0.62

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

Other links and lift over

dbSNP: rs375890125; hg19: chr16-31367990;