10-80155860-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145868.2(ANXA11):ā€‹c.1511A>Gā€‹(p.Asn504Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

ANXA11
NM_145868.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31
Variant links:
Genes affected
ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14435324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANXA11NM_145868.2 linkuse as main transcriptc.1511A>G p.Asn504Ser missense_variant 16/16 ENST00000422982.8 NP_665875.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANXA11ENST00000422982.8 linkuse as main transcriptc.1511A>G p.Asn504Ser missense_variant 16/161 NM_145868.2 ENSP00000404412 P2P50995-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461866
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 09, 2021In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ANXA11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 504 of the ANXA11 protein (p.Asn504Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
T;T;.;T
Eigen
Benign
-0.10
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.83
.;.;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
0.54
N;N;.;N
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.19
N;N;.;N
REVEL
Benign
0.12
Sift
Benign
0.49
T;T;.;T
Sift4G
Benign
0.55
T;T;T;T
Polyphen
0.22
B;B;.;B
Vest4
0.14
MutPred
0.37
Gain of disorder (P = 0.0255);Gain of disorder (P = 0.0255);.;Gain of disorder (P = 0.0255);
MVP
0.19
MPC
0.064
ClinPred
0.54
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-81915616; API