1-150984059-G-T

Variant names:

• chr1-150984059-G-T
• rs147042782
• NM_003568.3:c.257G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003568.3(ANXA9):​c.257G>T​(p.Arg86Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,610,884 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000098 (2 hom.)
• Consequence: ANXA9 NM_003568.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01903534).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003568.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA9	NM_003568.3	MANE Select	c.257G>T	p.Arg86Leu	missense	Exon 5 of 14	NP_003559.2	O76027

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA9	ENST00000368947.9	TSL:1 MANE Select	c.257G>T	p.Arg86Leu	missense	Exon 5 of 14	ENSP00000357943.4	O76027
	ANXA9	ENST00000887888.1		c.257G>T	p.Arg86Leu	missense	Exon 6 of 15	ENSP00000557947.1
	ANXA9	ENST00000887895.1		c.257G>T	p.Arg86Leu	missense	Exon 4 of 13	ENSP00000557954.1

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000207 AC: 51 AN: 246012 AF XY: 0.000158

Gnomad AFR exome AF: 0.00288

Gnomad AMR exome AF: 0.0000905

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.0000980 AC: 143 AN: 1458632 Hom.: 2 Cov.: 31 AF XY: 0.0000661 AC XY: 48 AN XY: 725662

African (AFR) AF: 0.00367 AC: 122 AN: 33284

American (AMR) AF: 0.000161 AC: 7 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110998

Other (OTH) AF: 0.000166 AC: 10 AN: 60238

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.000739 AC XY: 55 AN XY: 74452

African (AFR) AF: 0.00284 AC: 118 AN: 41548

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00104

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000255 AC: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00071	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.075	N
PhyloP100		4.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.099
Sift	Benign	0.085	T
Sift4G	Benign	0.72	T
Polyphen		0.65	P
Vest4		0.73
MVP		0.32
MPC		0.075
ClinPred		0.024	T
GERP RS		5.5
Varity_R		0.16
gMVP		0.35
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs147042782; hg19: chr1-150956535;