chr3-37503251-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002207.3(ITGA9):ā€‹c.686A>Gā€‹(p.Asn229Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

ITGA9
NM_002207.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19337812).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGA9NM_002207.3 linkuse as main transcriptc.686A>G p.Asn229Ser missense_variant 6/28 ENST00000264741.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGA9ENST00000264741.10 linkuse as main transcriptc.686A>G p.Asn229Ser missense_variant 6/281 NM_002207.3 P1
ITGA9ENST00000422441.5 linkuse as main transcriptc.686A>G p.Asn229Ser missense_variant 6/161

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461822
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378

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 GeneticsDec 20, 2023The c.686A>G (p.N229S) alteration is located in exon 6 (coding exon 6) of the ITGA9 gene. This alteration results from a A to G substitution at nucleotide position 686, causing the asparagine (N) at amino acid position 229 to be replaced by a serine (S). 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
0.080
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.033
T;T
Eigen
Benign
0.11
Eigen_PC
Benign
0.22
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.12
Sift
Benign
0.075
T;T
Sift4G
Uncertain
0.022
D;D
Polyphen
0.60
P;B
Vest4
0.35
MutPred
0.56
Gain of catalytic residue at N229 (P = 0.0598);Gain of catalytic residue at N229 (P = 0.0598);
MVP
0.48
MPC
0.21
ClinPred
0.86
D
GERP RS
5.8
Varity_R
0.13
gMVP
0.49

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: rs1053181052; hg19: chr3-37544742; API