chr16-31360064-G-T

Variant names:

• chr16-31360064-G-T
• NM_000887.5:c.706G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000887.5(ITGAX):​c.706G>T​(p.Val236Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ITGAX NM_000887.5 missense, splice_region
• Scores: Splicing: ADA: 0.0007144
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14377311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.706G>T	p.Val236Leu	missense_variant, splice_region_variant	Exon 7 of 30	ENST00000268296.9	NP_000878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.706G>T	p.Val236Leu	missense_variant, splice_region_variant	Exon 7 of 30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.706G>T	p.Val236Leu	missense_variant, splice_region_variant	Exon 7 of 31	1		ENSP00000454623.1
ITGAX	ENST00000571644.1	n.128G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 22	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457210 Hom.: 0 Cov.: 34 AF XY: 0.00000414 AC XY: 3 AN XY: 725026

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.92	L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.21	T;T
Polyphen		0.48	P;.
Vest4		0.092
MutPred		0.63		Gain of catalytic residue at V236 (P = 0.0191);Gain of catalytic residue at V236 (P = 0.0191);
MVP		0.49
MPC		0.21
ClinPred		0.15	T
GERP RS		-1.6
Varity_R		0.29
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00071
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31371385;