3-37732740-T-A

Variant summary

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

The NM_002207.3(ITGA9):​c.2096T>A​(p.Leu699Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ITGA9
NM_002207.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45
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-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

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=0.42180717).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGA9NM_002207.3 linkc.2096T>A p.Leu699Gln missense_variant Exon 19 of 28 ENST00000264741.10 NP_002198.2 Q13797Q8N6H6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGA9ENST00000264741.10 linkc.2096T>A p.Leu699Gln missense_variant Exon 19 of 28 1 NM_002207.3 ENSP00000264741.5 Q13797

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458830
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725162
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2096T>A (p.L699Q) alteration is located in exon 19 (coding exon 19) of the ITGA9 gene. This alteration results from a T to A substitution at nucleotide position 2096, causing the leucine (L) at amino acid position 699 to be replaced by a glutamine (Q). 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
0.081
BayesDel_addAF
Uncertain
0.053
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.17
Sift
Benign
0.081
T
Sift4G
Benign
0.069
T
Polyphen
0.97
D
Vest4
0.44
MutPred
0.45
Gain of disorder (P = 0.0568);
MVP
0.58
MPC
0.71
ClinPred
0.94
D
GERP RS
4.6
Varity_R
0.21
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

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

Other links and lift over

dbSNP: rs917137238; hg19: chr3-37774231; API