1-150983422-A-G

Variant summary

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

The NM_003568.3(ANXA9):ā€‹c.160A>Gā€‹(p.Ile54Val) variant causes a missense change. The variant allele was found at a frequency of 0.000259 in 1,611,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00036 ( 0 hom., cov: 32)
Exomes š‘“: 0.00025 ( 1 hom. )

Consequence

ANXA9
NM_003568.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25
Variant links:
Genes affected
ANXA9 (HGNC:547): (annexin A9) The annexins are a family of calcium-dependent phospholipid-binding proteins. Members of the annexin family contain 4 internal repeat domains, each of which includes a type II calcium-binding site. The calcium-binding sites are required for annexins to aggregate and cooperatively bind anionic phospholipids and extracellular matrix proteins. This gene encodes a divergent member of the annexin protein family in which all four homologous type II calcium-binding sites in the conserved tetrad core contain amino acid substitutions that ablate their function. However, structural analysis suggests that the conserved putative ion channel formed by the tetrad core is intact. [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=0.21541587).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANXA9NM_003568.3 linkuse as main transcriptc.160A>G p.Ile54Val missense_variant 4/14 ENST00000368947.9 NP_003559.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANXA9ENST00000368947.9 linkuse as main transcriptc.160A>G p.Ile54Val missense_variant 4/141 NM_003568.3 ENSP00000357943 P1
ANXA9ENST00000474997.1 linkuse as main transcriptn.313A>G non_coding_transcript_exon_variant 3/53

Frequencies

GnomAD3 genomes
AF:
0.000361
AC:
55
AN:
152250
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000749
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000263
AC:
64
AN:
243428
Hom.:
0
AF XY:
0.000281
AC XY:
37
AN XY:
131590
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000404
Gnomad FIN exome
AF:
0.0000976
Gnomad NFE exome
AF:
0.000428
Gnomad OTH exome
AF:
0.000506
GnomAD4 exome
AF:
0.000249
AC:
363
AN:
1459106
Hom.:
1
Cov.:
31
AF XY:
0.000269
AC XY:
195
AN XY:
725554
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000451
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000572
Gnomad4 FIN exome
AF:
0.000376
Gnomad4 NFE exome
AF:
0.000254
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000361
AC:
55
AN:
152368
Hom.:
0
Cov.:
32
AF XY:
0.000349
AC XY:
26
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.000750
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000400
Hom.:
0
Bravo
AF:
0.000193
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000297
AC:
36
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsSep 01, 2021The c.160A>G (p.I54V) alteration is located in exon 4 (coding exon 2) of the ANXA9 gene. This alteration results from a A to G substitution at nucleotide position 160, causing the isoleucine (I) at amino acid position 54 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
0.10
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0087
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
0.54
D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.14
Sift
Benign
0.067
T
Sift4G
Uncertain
0.060
T
Polyphen
0.90
P
Vest4
0.41
MVP
0.25
MPC
0.30
ClinPred
0.11
T
GERP RS
5.1
Varity_R
0.076
gMVP
0.34

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: rs200920607; hg19: chr1-150955898; API