chr4-78595828-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005139.3(ANXA3):c.575C>A(p.Thr192Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,611,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
ANXA3
NM_005139.3 missense
NM_005139.3 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 6.21
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.575C>A | p.Thr192Lys | missense_variant | 9/13 | ENST00000264908.11 | |
ANXA3 | XM_047450154.1 | c.575C>A | p.Thr192Lys | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA3 | ENST00000264908.11 | c.575C>A | p.Thr192Lys | missense_variant | 9/13 | 1 | NM_005139.3 | P1 | |
ANXA3 | ENST00000503570.6 | c.458C>A | p.Thr153Lys | missense_variant | 10/14 | 5 | |||
ANXA3 | ENST00000512884.5 | c.458C>A | p.Thr153Lys | missense_variant | 8/12 | 5 | |||
ANXA3 | ENST00000512542.5 | c.107C>A | p.Thr36Lys | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251022Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135666
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1459572Hom.: 0 Cov.: 28 AF XY: 0.0000151 AC XY: 11AN XY: 726248
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74456
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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 | Dec 08, 2023 | The c.575C>A (p.T192K) alteration is located in exon 9 (coding exon 8) of the ANXA3 gene. This alteration results from a C to A substitution at nucleotide position 575, causing the threonine (T) at amino acid position 192 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;.
Vest4
MutPred
Gain of ubiquitination at T192 (P = 0.023);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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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