NM_002207.3:c.20C>A

Variant names:

• chr3-37452394-C-A
• rs901587692
• NM_002207.3:c.20C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002207.3(ITGA9):​c.20C>A​(p.Pro7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000834 in 1,199,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. P7R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06462267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002207.3. 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
	ITGA9	NM_002207.3	MANE Select	c.20C>A	p.Pro7Gln	missense	Exon 1 of 28	NP_002198.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.20C>A	p.Pro7Gln	missense	Exon 1 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000422441.5	TSL:1	c.20C>A	p.Pro7Gln	missense	Exon 1 of 16	ENSP00000397258.1	E9PDS3
	ITGA9	ENST00000921363.1		c.20C>A	p.Pro7Gln	missense	Exon 1 of 28	ENSP00000591422.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.34e-7 AC: 1 AN: 1199472 Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1 AN XY: 586800

African (AFR) AF: 0.00 AC: 0 AN: 23680

American (AMR) AF: 0.00 AC: 0 AN: 13686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16754

East Asian (EAS) AF: 0.00 AC: 0 AN: 25070

South Asian (SAS) AF: 0.00 AC: 0 AN: 52918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983648

Other (OTH) AF: 0.0000209 AC: 1 AN: 47806

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.9
DANN	Benign	0.82
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.22
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.087
Sift	Benign	0.092	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.37		Gain of helix (P = 0.0078)
MVP		0.22
MPC		1.5
ClinPred		0.068	T
GERP RS		-1.8
PromoterAI		-0.088	Neutral
Varity_R		0.027
gMVP		0.36
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs901587692; hg19: chr3-37493885;