rs267733

Variant names:

• chr1-150986360-A-G
• rs267733
• NM_003568.3:c.497A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003568.3(ANXA9):​c.497A>G​(p.Asp166Gly) variant causes a missense change. The variant allele was found at a frequency of 0.142 in 1,613,636 control chromosomes in the GnomAD database, including 17,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1227 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16393 hom.)
• Consequence: ANXA9 NM_003568.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 104 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023424923).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA9	NM_003568.3	c.497A>G	p.Asp166Gly	missense_variant	Exon 8 of 14	ENST00000368947.9	NP_003559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA9	ENST00000368947.9	c.497A>G	p.Asp166Gly	missense_variant	Exon 8 of 14	1	NM_003568.3	ENSP00000357943.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17805 AN: 152098 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.118 AC: 29474 AN: 250636 AF XY: 0.118

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.0790

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.0341

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.145 AC: 211818 AN: 1461420 Hom.: 16393 Cov.: 32 AF XY: 0.143 AC XY: 104304 AN XY: 727032

African (AFR) AF: 0.0545 AC: 1826 AN: 33476

American (AMR) AF: 0.0810 AC: 3622 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4353 AN: 26134

East Asian (EAS) AF: 0.0426 AC: 1692 AN: 39700

South Asian (SAS) AF: 0.0724 AC: 6248 AN: 86254

European-Finnish (FIN) AF: 0.145 AC: 7722 AN: 53398

Middle Eastern (MID) AF: 0.160 AC: 925 AN: 5764

European-Non Finnish (NFE) AF: 0.159 AC: 177237 AN: 1111602

Other (OTH) AF: 0.136 AC: 8193 AN: 60380

GnomAD4 genome AF: 0.117 AC: 17801 AN: 152216 Hom.: 1227 Cov.: 32 AF XY: 0.115 AC XY: 8587 AN XY: 74416

African (AFR) AF: 0.0608 AC: 2527 AN: 41540

American (AMR) AF: 0.100 AC: 1530 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5180

South Asian (SAS) AF: 0.0628 AC: 303 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10661 AN: 68004

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.142 Hom.: 7840

Bravo AF: 0.112

TwinsUK AF: 0.158 AC: 586

ALSPAC AF: 0.145 AC: 559

ESP6500AA AF: 0.0615 AC: 271

ESP6500EA AF: 0.155 AC: 1332

ExAC AF: 0.116 AC: 14133

Asia WGS AF: 0.0470 AC: 166 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		4.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.058	T
Polyphen		0.99	D
Vest4		0.27
MPC		0.39
ClinPred		0.042	T
GERP RS		5.1
Varity_R		0.80
gMVP		0.69
Mutation Taster		=88/12	polymorphism (auto)

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

Other links and lift over

dbSNP: rs267733; hg19: chr1-150958836; COSMIC: COSV64484673; COSMIC: COSV64484673;