rs267733

Positions:

• chr1-150986360-A-G

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANXA9	NM_003568.3	c.497A>G	p.Asp166Gly	missense_variant	8/14	ENST00000368947.9	NP_003559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA9	ENST00000368947.9	c.497A>G	p.Asp166Gly	missense_variant	8/14	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

GnomAD3 exomes AF: 0.118 AC: 29474 AN: 250636 Hom.: 2036 AF XY: 0.118 AC XY: 15977 AN XY: 135458

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 SAS exome AF: 0.0714

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

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0426

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.136

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

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0259

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.127

Alfa AF: 0.145 Hom.: 4390

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
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

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

Other links and lift over

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