chr8-123688898-C-T

Variant names:

• chr8-123688898-C-T
• rs144282673
• NM_004306.4:c.691G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004306.4(ANXA13):​c.691G>A​(p.Asp231Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (2 hom.)
• Consequence: ANXA13 NM_004306.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07942939).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA13	NM_004306.4	MANE Select	c.691G>A	p.Asp231Asn	missense	Exon 9 of 11	NP_004297.2	P27216-1
	ANXA13	NM_001003954.3		c.814G>A	p.Asp272Asn	missense	Exon 10 of 12	NP_001003954.1	P27216-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA13	ENST00000419625.6	TSL:1 MANE Select	c.691G>A	p.Asp231Asn	missense	Exon 9 of 11	ENSP00000390809.1	P27216-1
	ANXA13	ENST00000262219.10	TSL:1	c.814G>A	p.Asp272Asn	missense	Exon 10 of 12	ENSP00000262219.6	P27216-2
	ANXA13	ENST00000862979.1		c.745G>A	p.Asp249Asn	missense	Exon 9 of 11	ENSP00000533038.1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000453 AC: 114 AN: 251456 AF XY: 0.000500

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.000343 AC: 501 AN: 1461650 Hom.: 2 Cov.: 30 AF XY: 0.000369 AC XY: 268 AN XY: 727146

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.000604 AC: 27 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39692

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000335 AC: 372 AN: 1111864

Other (OTH) AF: 0.000480 AC: 29 AN: 60380

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74442

African (AFR) AF: 0.0000481 AC: 2 AN: 41542

American (AMR) AF: 0.000458 AC: 7 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68010

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000514 Hom.: 0

Bravo AF: 0.000412

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000428 AC: 52

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000771

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	0.19
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.8
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.087
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.54	P
Vest4		0.35
MVP		0.45
MPC		0.14
ClinPred		0.039	T
GERP RS		3.9
Varity_R		0.22
gMVP		0.87
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs144282673; hg19: chr8-124701138; COSMIC: COSV51622564;