2-111792471-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_022662.4(ANAPC1):c.4603G>A(p.Val1535Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ANAPC1
NM_022662.4 missense
NM_022662.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
ANAPC1 (HGNC:19988): (anaphase promoting complex subunit 1) This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 2011]
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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;
PP2
Missense variant where missense usually causes diseases, ANAPC1
BP4
Computational evidence support a benign effect (MetaRNN=0.350433).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANAPC1 | NM_022662.4 | c.4603G>A | p.Val1535Ile | missense_variant | 38/48 | ENST00000341068.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANAPC1 | ENST00000341068.8 | c.4603G>A | p.Val1535Ile | missense_variant | 38/48 | 1 | NM_022662.4 | P1 | |
ANAPC1 | ENST00000427997.5 | c.3208G>A | p.Val1070Ile | missense_variant | 27/37 | 1 | |||
ANAPC1 | ENST00000464695.1 | n.453G>A | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes Cov.: 27
GnomAD3 genomes
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27
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250724Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135582
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461654Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727138
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GnomAD4 genome Cov.: 27
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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 | Aug 12, 2021 | The c.4603G>A (p.V1535I) alteration is located in exon 38 (coding exon 37) of the ANAPC1 gene. This alteration results from a G to A substitution at nucleotide position 4603, causing the valine (V) at amino acid position 1535 to be replaced by an isoleucine (I). 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
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K1534 (P = 0.143);
MVP
ClinPred
D
GERP RS
Varity_R
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