chr4-78582249-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005139.3(ANXA3):c.271C>G(p.Pro91Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
ANXA3
NM_005139.3 missense
NM_005139.3 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.37
Genes affected
ANXA3 (HGNC:541): (annexin A3) 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. This protein functions in the inhibition of phopholipase A2 and cleavage of inositol 1,2-cyclic phosphate to form inositol 1-phosphate. This protein may also play a role in anti-coagulation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANXA3 | NM_005139.3 | c.271C>G | p.Pro91Ala | missense_variant | 5/13 | ENST00000264908.11 | |
ANXA3 | XM_047450154.1 | c.271C>G | p.Pro91Ala | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA3 | ENST00000264908.11 | c.271C>G | p.Pro91Ala | missense_variant | 5/13 | 1 | NM_005139.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250912Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135578
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461310Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726934
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726934
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.271C>G (p.P91A) alteration is located in exon 5 (coding exon 4) of the ANXA3 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the proline (P) at amino acid position 91 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;D;D;D
Sift4G
Benign
T;T;T;D;D;T
Polyphen
D;.;.;.;.;.
Vest4
MutPred
Loss of catalytic residue at P90 (P = 0.0185);.;.;Loss of catalytic residue at P90 (P = 0.0185);Loss of catalytic residue at P90 (P = 0.0185);Loss of catalytic residue at P90 (P = 0.0185);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at