chr4-78597340-T-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005139.3(ANXA3):c.656T>A(p.Ile219Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00428 in 1,609,370 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.022 ( 119 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 128 hom. )
Consequence
ANXA3
NM_005139.3 missense
NM_005139.3 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 6.03
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.004128784).
BP6
Variant 4-78597340-T-A is Benign according to our data. Variant chr4-78597340-T-A is described in ClinVar as [Benign]. Clinvar id is 775990.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANXA3 | NM_005139.3 | c.656T>A | p.Ile219Asn | missense_variant | 10/13 | ENST00000264908.11 | |
ANXA3 | XM_047450154.1 | c.656T>A | p.Ile219Asn | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANXA3 | ENST00000264908.11 | c.656T>A | p.Ile219Asn | missense_variant | 10/13 | 1 | NM_005139.3 | P1 | |
ANXA3 | ENST00000503570.6 | c.539T>A | p.Ile180Asn | missense_variant | 11/14 | 5 | |||
ANXA3 | ENST00000512884.5 | c.539T>A | p.Ile180Asn | missense_variant | 9/12 | 5 | |||
ANXA3 | ENST00000505805.1 | n.268T>A | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0224 AC: 3412AN: 152212Hom.: 118 Cov.: 32
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GnomAD3 exomes AF: 0.00589 AC: 1459AN: 247502Hom.: 39 AF XY: 0.00429 AC XY: 573AN XY: 133616
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GnomAD4 exome AF: 0.00238 AC: 3464AN: 1457040Hom.: 128 Cov.: 28 AF XY: 0.00200 AC XY: 1448AN XY: 724872
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GnomAD4 genome AF: 0.0225 AC: 3422AN: 152330Hom.: 119 Cov.: 32 AF XY: 0.0217 AC XY: 1617AN XY: 74496
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 10, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
T
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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