chr1-183648499-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_203454.3(APOBEC4):c.283G>A(p.Glu95Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
APOBEC4
NM_203454.3 missense
NM_203454.3 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 5.08
Genes affected
APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a active_site Proton donor (size 0) in uniprot entity ABEC4_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.866
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOBEC4 | NM_203454.3 | c.283G>A | p.Glu95Lys | missense_variant | 2/2 | ENST00000308641.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOBEC4 | ENST00000308641.6 | c.283G>A | p.Glu95Lys | missense_variant | 2/2 | 1 | NM_203454.3 | P1 | |
RGL1 | ENST00000304685.8 | c.-33+11998C>T | intron_variant | 1 | |||||
APOBEC4 | ENST00000481562.1 | n.246-702G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251170Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135754
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727248
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74448
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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 | Oct 16, 2023 | The c.283G>A (p.E95K) alteration is located in exon 2 (coding exon 1) of the APOBEC4 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the glutamic acid (E) at amino acid position 95 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
Pathogenic
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
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