Genetic Variant NM_181773.5:c.313G>C (chr22-39101399-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181773.5(APOBEC3H):c.313G>C(p.Gly105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,610,706 control chromosomes in the GnomAD database, including 187,811 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G105V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.56 ( 25134 hom., cov: 22)

Exomes 𝑓: 0.47 ( 162677 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Publications

68 publications found

Variant links:

Genes affected

APOBEC3H (HGNC:24100): (apolipoprotein B mRNA editing enzyme catalytic subunit 3H) This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

APOBEC3H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.6928052E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5 link	c.313G>C	p.Gly105Arg	missense_variant	Exon 3 of 5	ENST00000442487.8	NP_861438.3	Q6NTF7-3B7TQM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8 link	c.313G>C	p.Gly105Arg	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3		Q6NTF7-3

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

83026

AN:

148862

Hom.:

25099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.541

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.502

GnomAD2 exomes

AF:

0.470

AC:

117985

AN:

251172

AF XY:

0.470

show subpopulations

Gnomad AFR exome

AF:

0.819

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.465

AC:

680340

AN:

1461740

Hom.:

162677

Cov.:

AF XY:

0.466

AC XY:

338653

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.829

AC:

27743

AN:

33478

American (AMR)

AF:

0.353

AC:

15804

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

11915

AN:

26136

East Asian (EAS)

AF:

0.318

AC:

12640

AN:

39700

South Asian (SAS)

AF:

0.488

AC:

42111

AN:

86254

European-Finnish (FIN)

AF:

0.544

AC:

29056

AN:

53398

Middle Eastern (MID)

AF:

0.493

AC:

2825

AN:

5736

European-Non Finnish (NFE)

AF:

0.459

AC:

509882

AN:

1111926

Other (OTH)

AF:

0.470

AC:

28364

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

22002

44004

66005

88007

110009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15256

30512

45768

61024

76280

<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:

0.558

AC:

83112

AN:

148966

Hom.:

25134

Cov.:

AF XY:

0.556

AC XY:

40337

AN XY:

72512

show subpopulations

African (AFR)

AF:

0.816

AC:

33100

AN:

40544

American (AMR)

AF:

0.417

AC:

6217

AN:

14892

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1566

AN:

3440

East Asian (EAS)

AF:

0.335

AC:

1662

AN:

4964

South Asian (SAS)

AF:

0.475

AC:

2215

AN:

4660

European-Finnish (FIN)

AF:

0.541

AC:

5512

AN:

10184

Middle Eastern (MID)

AF:

0.479

AC:

137

AN:

286

European-Non Finnish (NFE)

AF:

0.465

AC:

31207

AN:

67042

Other (OTH)

AF:

0.498

AC:

1025

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

1502

3004

4505

6007

7509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.335

Hom.:

4607

Bravo

AF:

0.554

TwinsUK

AF:

0.461

AC:

1710

ALSPAC

AF:

0.455

AC:

1755

ESP6500AA

AF:

0.811

AC:

3573

ESP6500EA

AF:

0.461

AC:

3964

ExAC

AF:

0.481

AC:

58450

Asia WGS

AF:

0.388

AC:

1275

AN:

3278

EpiCase

AF:

0.457

EpiControl

AF:

0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0010

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.0027

.;T;.;T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.052

T;T;T;.;T;.

MetaRNN

Benign

0.0000017

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.6

.;N;N;N;N;.

PhyloP100

-1.6

PrimateAI

Benign

0.23

PROVEAN

Benign

3.4

N;.;N;N;N;.

REVEL

Benign

0.068

Sift

Benign

1.0

T;.;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Vest4

0.051

MPC

0.22

ClinPred

0.0081

GERP RS

-4.6

Varity_R

0.13

gMVP

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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