22-39086481-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_021822.4(APOBEC3G):ā€‹c.938G>Cā€‹(p.Arg313Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

APOBEC3G
NM_021822.4 missense

Scores

5
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.28
Variant links:
Genes affected
APOBEC3G (HGNC:17357): (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. The protein encoded by this gene catalyzes site-specific deamination of both RNA and single-stranded DNA. The encoded protein has been found to be a specific inhibitor of human immunodeficiency virus-1 (HIV-1) infectivity. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a mutagenesis_site Abolishes enzyme activity. (size 0) in uniprot entity ABC3G_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBEC3GNM_021822.4 linkc.938G>C p.Arg313Pro missense_variant Exon 6 of 8 ENST00000407997.4 NP_068594.1 Q9HC16-1
APOBEC3GNM_001349436.1 linkc.905G>C p.Arg302Pro missense_variant Exon 6 of 8 NP_001336365.1
APOBEC3GNM_001349437.2 linkc.737G>C p.Arg246Pro missense_variant Exon 5 of 7 NP_001336366.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBEC3GENST00000407997.4 linkc.938G>C p.Arg313Pro missense_variant Exon 6 of 8 1 NM_021822.4 ENSP00000385057.3 Q9HC16-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461860
Hom.:
0
Cov.:
34
AF XY:
0.0000261
AC XY:
19
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.39
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.038
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Benign
-0.46
T
MutationAssessor
Pathogenic
3.7
H
PROVEAN
Pathogenic
-5.8
D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.74
MutPred
0.95
Loss of MoRF binding (P = 0.075);
MVP
0.81
MPC
0.86
ClinPred
0.99
D
GERP RS
1.6
Varity_R
0.98
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs542681958; hg19: chr22-39482486; API