rs267731

Positions:

• chr1-150983106-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BS1 BS2

The NM_003568.3(ANXA9):​c.1A>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,560 control chromosomes in the GnomAD database, including 1,105 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 0.025 (76 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1029 hom.)
• Consequence: ANXA9 NM_003568.3 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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]

ANXA9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0254 (3855/152040) while in subpopulation NFE AF= 0.0394 (2678/67964). AF 95% confidence interval is 0.0382. There are 76 homozygotes in gnomad4. There are 1877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA9	NM_003568.3	c.1A>G	p.Met1?	start_lost	3/14	ENST00000368947.9	NP_003559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA9	ENST00000368947.9	c.1A>G	p.Met1?	start_lost	3/14	1	NM_003568.3	ENSP00000357943.4
ANXA9	ENST00000474997.1	n.229-232A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3853 AN: 151922 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.00573

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00416

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.0250 AC: 6264 AN: 251000 Hom.: 111 AF XY: 0.0244 AC XY: 3306 AN XY: 135668

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.0169

Gnomad ASJ exome AF: 0.0194

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00379

Gnomad FIN exome AF: 0.0339

Gnomad NFE exome AF: 0.0386

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.0341 AC: 49809 AN: 1461520 Hom.: 1029 Cov.: 31 AF XY: 0.0332 AC XY: 24124 AN XY: 727072

Gnomad4 AFR exome AF: 0.00517

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00380

Gnomad4 FIN exome AF: 0.0323

Gnomad4 NFE exome AF: 0.0401

Gnomad4 OTH exome AF: 0.0284

GnomAD4 genome AF: 0.0254 AC: 3855 AN: 152040 Hom.: 76 Cov.: 32 AF XY: 0.0253 AC XY: 1877 AN XY: 74324

Gnomad4 AFR AF: 0.00571

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00417

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0334 Hom.: 151

Bravo AF: 0.0238

TwinsUK AF: 0.0380 AC: 141

ALSPAC AF: 0.0348 AC: 134

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.0381 AC: 328

ExAC AF: 0.0246 AC: 2984

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0371

EpiControl AF: 0.0385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.91	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.15
Sift	Benign	0.049	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.28
ClinPred		0.020	T
GERP RS		3.9
Varity_R		0.28
gMVP		0.56

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

Other links and lift over

dbSNP: rs267731; hg19: chr1-150955582;