Genetic Variant NM_021822.4:c.357T>C (chr22-39081118-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021822.4(APOBEC3G):c.357T>C(p.Phe119Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,614,034 control chromosomes in the GnomAD database, including 136,188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 9178 hom., cov: 32)

Exomes 𝑓: 0.41 ( 127010 hom. )

Consequence

APOBEC3G
NM_021822.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40

Publications

37 publications found

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]

APOBEC3G links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4 link	c.357T>C	p.Phe119Phe	synonymous_variant	Exon 3 of 8	ENST00000407997.4	NP_068594.1	Q9HC16-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4 link	c.357T>C	p.Phe119Phe	synonymous_variant	Exon 3 of 8	1	NM_021822.4	ENSP00000385057.3		Q9HC16-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47743

AN:

152058

Hom.:

9181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0845

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.374

AC:

93928

AN:

251462

AF XY:

0.386

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.410

AC:

599417

AN:

1461858

Hom.:

127010

Cov.:

AF XY:

0.412

AC XY:

299924

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0691

AC:

2315

AN:

33480

American (AMR)

AF:

0.384

AC:

17169

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

11772

AN:

26136

East Asian (EAS)

AF:

0.244

AC:

9677

AN:

39700

South Asian (SAS)

AF:

0.433

AC:

37388

AN:

86254

European-Finnish (FIN)

AF:

0.290

AC:

15471

AN:

53420

Middle Eastern (MID)

AF:

0.455

AC:

2621

AN:

5766

European-Non Finnish (NFE)

AF:

0.431

AC:

479083

AN:

1111986

Other (OTH)

AF:

0.396

AC:

23921

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

23260

46520

69780

93040

116300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14440

28880

43320

57760

72200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.314

AC:

47720

AN:

152176

Hom.:

9178

Cov.:

AF XY:

0.312

AC XY:

23211

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0842

AC:

3498

AN:

41548

American (AMR)

AF:

0.411

AC:

6276

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1552

AN:

3464

East Asian (EAS)

AF:

0.231

AC:

1196

AN:

5178

South Asian (SAS)

AF:

0.419

AC:

2019

AN:

4820

European-Finnish (FIN)

AF:

0.291

AC:

3088

AN:

10604

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28810

AN:

67964

Other (OTH)

AF:

0.376

AC:

795

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1577

3154

4730

6307

7884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

39800

Bravo

AF:

0.310

Asia WGS

AF:

0.301

AC:

1047

AN:

3478

EpiCase

AF:

0.444

EpiControl

AF:

0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.51

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over