chr4-25396857-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_013367.3(ANAPC4):c.1172C>T(p.Thr391Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,508 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ANAPC4
NM_013367.3 missense
NM_013367.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.56
Genes affected
ANAPC4 (HGNC:19990): (anaphase promoting complex subunit 4) A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40413767).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANAPC4 | NM_013367.3 | c.1172C>T | p.Thr391Ile | missense_variant | 16/29 | ENST00000315368.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANAPC4 | ENST00000315368.8 | c.1172C>T | p.Thr391Ile | missense_variant | 16/29 | 1 | NM_013367.3 | P4 | |
ANAPC4 | ENST00000510092.5 | c.1172C>T | p.Thr391Ile | missense_variant | 16/29 | 5 | A1 | ||
ANAPC4 | ENST00000503805.5 | n.259C>T | non_coding_transcript_exon_variant | 3/8 | 4 | ||||
ANAPC4 | ENST00000505842.5 | n.56C>T | non_coding_transcript_exon_variant | 2/8 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460508Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726578
GnomAD4 exome
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2
AN:
1460508
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Cov.:
31
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2
AN XY:
726578
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
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Asia WGS
AF:
AC:
1
AN:
3478
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 | Jun 29, 2023 | The c.1172C>T (p.T391I) alteration is located in exon 16 (coding exon 15) of the ANAPC4 gene. This alteration results from a C to T substitution at nucleotide position 1172, causing the threonine (T) at amino acid position 391 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of catalytic residue at T391 (P = 0.029);Loss of catalytic residue at T391 (P = 0.029);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at