chr3-37533460-G-T

Position:

• chr3-37533460-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002207.3(ITGA9):​c.1520G>T​(p.Gly507Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G507E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

Genes affected

ITGA9 (HGNC:6145): (integrin subunit alpha 9) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA9	NM_002207.3	c.1520G>T	p.Gly507Val	missense_variant	14/28	ENST00000264741.10	NP_002198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10	c.1520G>T	p.Gly507Val	missense_variant	14/28	1	NM_002207.3	ENSP00000264741.5
ITGA9	ENST00000422441.5	c.1520G>T	p.Gly507Val	missense_variant	14/16	1		ENSP00000397258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;P
Vest4		0.69
MutPred		0.65		Loss of methylation at K503 (P = 0.0703);Loss of methylation at K503 (P = 0.0703);
MVP		0.70
MPC		0.83
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.86
gMVP		0.78

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: rs267561; hg19: chr3-37574951;