dbSNP rs139298: APOBEC3H:p.Lys121Glu (chr22-39101447-A-G) – 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.361A>G(p.Lys121Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,609,282 control chromosomes in the GnomAD database, including 190,935 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.

Frequency

Genomes: 𝑓 0.56 ( 25247 hom., cov: 21)

Exomes 𝑓: 0.47 ( 165688 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

44 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=3.0716478E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5 link	c.361A>G	p.Lys121Glu	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.361A>G	p.Lys121Glu	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3		Q6NTF7-3

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

83167

AN:

147912

Hom.:

25210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.505

GnomAD2 exomes

AF:

0.474

AC:

118877

AN:

250842

AF XY:

0.475

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.545

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.470

AC:

686725

AN:

1461250

Hom.:

165688

Cov.:

AF XY:

0.470

AC XY:

341894

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.830

AC:

27770

AN:

33466

American (AMR)

AF:

0.357

AC:

15948

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

12042

AN:

26130

East Asian (EAS)

AF:

0.318

AC:

12642

AN:

39696

South Asian (SAS)

AF:

0.494

AC:

42621

AN:

86234

European-Finnish (FIN)

AF:

0.544

AC:

29030

AN:

53330

Middle Eastern (MID)

AF:

0.499

AC:

2773

AN:

5556

European-Non Finnish (NFE)

AF:

0.463

AC:

515265

AN:

1111790

Other (OTH)

AF:

0.475

AC:

28634

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

19620

39241

58861

78482

98102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15362

30724

46086

61448

76810

<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:

0.562

AC:

83260

AN:

148032

Hom.:

25247

Cov.:

AF XY:

0.561

AC XY:

40398

AN XY:

72014

show subpopulations

African (AFR)

AF:

0.818

AC:

32872

AN:

40182

American (AMR)

AF:

0.426

AC:

6268

AN:

14728

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1585

AN:

3436

East Asian (EAS)

AF:

0.335

AC:

1662

AN:

4954

South Asian (SAS)

AF:

0.486

AC:

2216

AN:

4556

European-Finnish (FIN)

AF:

0.543

AC:

5436

AN:

10014

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.471

AC:

31549

AN:

66932

Other (OTH)

AF:

0.500

AC:

1024

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.495

Hom.:

54722

Bravo

AF:

0.558

TwinsUK

AF:

0.459

AC:

1703

ALSPAC

AF:

0.453

AC:

1746

ESP6500AA

AF:

0.807

AC:

3557

ESP6500EA

AF:

0.456

AC:

3922

ExAC

AF:

0.485

AC:

58838

Asia WGS

AF:

0.393

AC:

1345

AN:

3412

EpiCase

AF:

0.464

EpiControl

AF:

0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0020

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.0034

.;T;.;T;.;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.00082

LIST_S2

Benign

0.17

T;T;T;.;T;.

MetaRNN

Benign

0.0000031

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;N;N;N;N;.

PhyloP100

-2.1

PrimateAI

Benign

0.25

PROVEAN

Benign

1.0

N;.;N;N;N;.

REVEL

Benign

0.053

Sift

Benign

1.0

T;.;T;T;T;.

Sift4G

Benign

0.64

T;T;T;T;T;T

Vest4

0.016

MPC

0.26

ClinPred

0.0019

GERP RS

-6.7

Varity_R

0.063

gMVP

0.16

Mutation Taster

=99/1

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