rs2294015

Positions:

• chr8-123684627-C-G
• chr8-123684627-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004306.4(ANXA13):​c.814G>C​(p.Val272Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V272I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANXA13 NM_004306.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12669289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA13	NM_004306.4	c.814G>C	p.Val272Leu	missense_variant	10/11	ENST00000419625.6
ANXA13	NM_001003954.3	c.937G>C	p.Val313Leu	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA13	ENST00000419625.6	c.814G>C	p.Val272Leu	missense_variant	10/11	1	NM_004306.4	P1
ANXA13	ENST00000262219.10	c.937G>C	p.Val313Leu	missense_variant	11/12	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.9
DANN	Benign	0.96
DEOGEN2	Benign	0.0070	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.033
Sift	Benign	0.13	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.37		.;Loss of sheet (P = 0.1158);
MVP		0.21
MPC		0.14
ClinPred		0.23	T
GERP RS		0.12
Varity_R		0.060
gMVP		0.37

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: rs2294015; hg19: chr8-124696867;