22-39086366-C-G

Variant names:

• chr22-39086366-C-G
• rs17496046
• NM_021822.4:c.823C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021822.4(APOBEC3G):​c.823C>G​(p.Gln275Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 1,613,934 control chromosomes in the GnomAD database, including 4,282 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (605 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3677 hom.)
• Consequence: APOBEC3G NM_021822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019907653).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.823C>G	p.Gln275Glu	missense_variant	Exon 6 of 8	ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.790C>G	p.Gln264Glu	missense_variant	Exon 6 of 8		NP_001336365.1
APOBEC3G	NM_001349437.2	c.622C>G	p.Gln208Glu	missense_variant	Exon 5 of 7		NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.823C>G	p.Gln275Glu	missense_variant	Exon 6 of 8	1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12497 AN: 152100 Hom.: 604 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0850

GnomAD2 exomes AF: 0.0562 AC: 14121 AN: 251392 AF XY: 0.0533

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0769

Gnomad EAS exome AF: 0.0175

Gnomad FIN exome AF: 0.0412

Gnomad NFE exome AF: 0.0682

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0661 AC: 96665 AN: 1461716 Hom.: 3677 Cov.: 34 AF XY: 0.0642 AC XY: 46713 AN XY: 727160

African (AFR) AF: 0.138 AC: 4629 AN: 33476

American (AMR) AF: 0.0400 AC: 1787 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 2104 AN: 26116

East Asian (EAS) AF: 0.0242 AC: 960 AN: 39698

South Asian (SAS) AF: 0.0163 AC: 1408 AN: 86248

European-Finnish (FIN) AF: 0.0446 AC: 2383 AN: 53406

Middle Eastern (MID) AF: 0.0590 AC: 340 AN: 5766

European-Non Finnish (NFE) AF: 0.0711 AC: 79040 AN: 1111904

Other (OTH) AF: 0.0665 AC: 4014 AN: 60388

GnomAD4 genome AF: 0.0822 AC: 12513 AN: 152218 Hom.: 605 Cov.: 32 AF XY: 0.0793 AC XY: 5900 AN XY: 74436

African (AFR) AF: 0.133 AC: 5522 AN: 41508

American (AMR) AF: 0.0629 AC: 961 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5190

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4826

European-Finnish (FIN) AF: 0.0425 AC: 451 AN: 10614

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0710 AC: 4829 AN: 68006

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0719 Hom.: 292

Bravo AF: 0.0875

TwinsUK AF: 0.0820 AC: 304

ALSPAC AF: 0.0698 AC: 269

ESP6500AA AF: 0.131 AC: 578

ESP6500EA AF: 0.0734 AC: 631

ExAC AF: 0.0573 AC: 6961

Asia WGS AF: 0.0310 AC: 107 AN: 3478

EpiCase AF: 0.0680

EpiControl AF: 0.0649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.2
DANN	Benign	0.72
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.082
Sift	Benign	0.21	T
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.038
MPC		0.75
ClinPred		0.011	T
GERP RS		0.43
Varity_R		0.39
gMVP		0.19
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17496046; hg19: chr22-39482371; COSMIC: COSV68470264; COSMIC: COSV68470264;