chr3-37481544-T-C

Variant summary

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

The NM_002207.3(ITGA9):​c.481T>C​(p.Phe161Leu) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ITGA9
NM_002207.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.60
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]

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=0.30474102).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGA9NM_002207.3 linkuse as main transcriptc.481T>C p.Phe161Leu missense_variant 4/28 ENST00000264741.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGA9ENST00000264741.10 linkuse as main transcriptc.481T>C p.Phe161Leu missense_variant 4/281 NM_002207.3 P1
ITGA9ENST00000422441.5 linkuse as main transcriptc.481T>C p.Phe161Leu missense_variant 4/161

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2023The c.481T>C (p.F161L) alteration is located in exon 4 (coding exon 4) of the ITGA9 gene. This alteration results from a T to C substitution at nucleotide position 481, causing the phenylalanine (F) at amino acid position 161 to be replaced by a leucine (L). 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
Pathogenic
0.84
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0063
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
0.053
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.36
.;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.66
N;N
REVEL
Benign
0.15
Sift
Benign
0.72
T;T
Sift4G
Benign
0.41
T;T
Polyphen
0.029
B;B
Vest4
0.47
MutPred
0.26
Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);
MVP
0.50
MPC
0.24
ClinPred
0.74
D
GERP RS
5.5
Varity_R
0.18
gMVP
0.84

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.

Other links and lift over

dbSNP: rs1698555180; hg19: chr3-37523035; API