chr8-123684627-C-T

Variant names:

• chr8-123684627-C-T
• rs2294015
• NM_004306.4:c.814G>A

Variant summary

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

The NM_004306.4(ANXA13):​c.814G>A​(p.Val272Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,612,152 control chromosomes in the GnomAD database, including 299,530 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (36135 hom., cov: 31)
  • Exomes 𝑓: 0.60 (263395 hom.)
• Consequence: ANXA13 NM_004306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 32 publications found

Genes affected

ANXA13 (HGNC:536): (annexin A13) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The specific function of this gene has not yet been determined; however, it is associated with the plasma membrane of undifferentiated, proliferating endothelial cells and differentiated villus enterocytes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ENSG00000253286 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.775247E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA13	NM_004306.4	MANE Select	c.814G>A	p.Val272Ile	missense	Exon 10 of 11	NP_004297.2
	ANXA13	NM_001003954.3		c.937G>A	p.Val313Ile	missense	Exon 11 of 12	NP_001003954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA13	ENST00000419625.6	TSL:1 MANE Select	c.814G>A	p.Val272Ile	missense	Exon 10 of 11	ENSP00000390809.1
	ANXA13	ENST00000262219.10	TSL:1	c.937G>A	p.Val313Ile	missense	Exon 11 of 12	ENSP00000262219.6
	ENSG00000253286	ENST00000836608.1		n.119-28065C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102784 AN: 151978 Hom.: 36080 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.635

GnomAD2 exomes AF: 0.617 AC: 155127 AN: 251374 AF XY: 0.616

Gnomad AFR exome AF: 0.886

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.623

GnomAD4 exome AF: 0.597 AC: 871455 AN: 1460056 Hom.: 263395 Cov.: 38 AF XY: 0.600 AC XY: 435526 AN XY: 726476

African (AFR) AF: 0.891 AC: 29826 AN: 33466

American (AMR) AF: 0.619 AC: 27651 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 14055 AN: 26130

East Asian (EAS) AF: 0.473 AC: 18765 AN: 39690

South Asian (SAS) AF: 0.697 AC: 60102 AN: 86222

European-Finnish (FIN) AF: 0.627 AC: 33471 AN: 53416

Middle Eastern (MID) AF: 0.636 AC: 3662 AN: 5762

European-Non Finnish (NFE) AF: 0.583 AC: 646904 AN: 1110318

Other (OTH) AF: 0.613 AC: 37019 AN: 60346

GnomAD4 genome AF: 0.677 AC: 102898 AN: 152096 Hom.: 36135 Cov.: 31 AF XY: 0.676 AC XY: 50260 AN XY: 74344

African (AFR) AF: 0.881 AC: 36565 AN: 41506

American (AMR) AF: 0.645 AC: 9854 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2571 AN: 5162

South Asian (SAS) AF: 0.708 AC: 3404 AN: 4810

European-Finnish (FIN) AF: 0.628 AC: 6638 AN: 10572

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39859 AN: 67992

Other (OTH) AF: 0.637 AC: 1344 AN: 2110

Alfa AF: 0.607 Hom.: 125451

Bravo AF: 0.681

TwinsUK AF: 0.584 AC: 2164

ALSPAC AF: 0.598 AC: 2306

ESP6500AA AF: 0.872 AC: 3843

ESP6500EA AF: 0.585 AC: 5029

ExAC AF: 0.624 AC: 75745

Asia WGS AF: 0.632 AC: 2200 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.51
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0000088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N
PhyloP100		0.74
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.11
ClinPred		0.0042	T
GERP RS		0.12
Varity_R		0.022
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

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: rs2294015; hg19: chr8-124696867; COSMIC: COSV51623558;