Genetic Variant ITGA9:p.Leu759Val (chr3-37741770-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002207.3(ITGA9):c.2275C>G(p.Leu759Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ITGA9
NM_002207.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

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]

ITGA9 links:

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ITGA9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3189292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3 link	c.2275C>G	p.Leu759Val	missense_variant	Exon 21 of 28	ENST00000264741.10	NP_002198.2	Q13797Q8N6H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 link	c.2275C>G	p.Leu759Val	missense_variant	Exon 21 of 28	1	NM_002207.3	ENSP00000264741.5		Q13797

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000599

AC:

AN:

250414

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461516

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000190

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2275C>G (p.L759V) alteration is located in exon 21 (coding exon 21) of the ITGA9 gene. This alteration results from a C to G substitution at nucleotide position 2275, causing the leucine (L) at amino acid position 759 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.10

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.025

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.70

REVEL

Benign

0.16

Sift

Benign

0.91

Sift4G

Benign

0.71

Polyphen

0.21

Vest4

0.71

MVP

0.34

MPC

0.77

ClinPred

0.036

GERP RS

5.2

Varity_R

0.13

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over