dbSNP rs139299: APOBEC3H:p.Lys121Asn (chr22-39101449-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.363G>C(p.Lys121Asn) 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 1,609,736 control chromosomes in the GnomAD database, including 190,903 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 ( 25222 hom., cov: 21)

Exomes 𝑓: 0.47 ( 165681 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

Publications

30 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=4.6781456E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5 link	c.363G>C	p.Lys121Asn	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.363G>C	p.Lys121Asn	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3		Q6NTF7-3

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

83144

AN:

148366

Hom.:

25185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.817

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.541

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.505

GnomAD2 exomes

AF:

0.474

AC:

118872

AN:

250840

AF XY:

0.475

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.461

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:

686712

AN:

1461252

Hom.:

165681

Cov.:

AF XY:

0.470

AC XY:

341879

AN XY:

726932

show subpopulations

African (AFR)

AF:

0.830

AC:

27768

AN:

33464

American (AMR)

AF:

0.357

AC:

15950

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

12042

AN:

26130

East Asian (EAS)

AF:

0.318

AC:

12642

AN:

39698

South Asian (SAS)

AF:

0.494

AC:

42617

AN:

86234

European-Finnish (FIN)

AF:

0.544

AC:

29031

AN:

53338

Middle Eastern (MID)

AF:

0.498

AC:

2760

AN:

5538

European-Non Finnish (NFE)

AF:

0.463

AC:

515267

AN:

1111798

Other (OTH)

AF:

0.475

AC:

28635

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

19789

39578

59368

79157

98946

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:

0.561

AC:

83237

AN:

148484

Hom.:

25222

Cov.:

AF XY:

0.559

AC XY:

40382

AN XY:

72258

show subpopulations

African (AFR)

AF:

0.817

AC:

32832

AN:

40188

American (AMR)

AF:

0.423

AC:

6265

AN:

14800

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1584

AN:

3450

East Asian (EAS)

AF:

0.332

AC:

1667

AN:

5014

South Asian (SAS)

AF:

0.483

AC:

2220

AN:

4594

European-Finnish (FIN)

AF:

0.541

AC:

5436

AN:

10054

Middle Eastern (MID)

AF:

0.497

AC:

144

AN:

290

European-Non Finnish (NFE)

AF:

0.470

AC:

31560

AN:

67156

Other (OTH)

AF:

0.500

AC:

1025

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

1500

3000

4500

6000

7500

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:

0.496

Hom.:

6256

Bravo

AF:

0.558

TwinsUK

AF:

0.458

AC:

1698

ALSPAC

AF:

0.453

AC:

1744

ESP6500AA

AF:

0.809

AC:

3564

ESP6500EA

AF:

0.457

AC:

3932

ExAC

AF:

0.485

AC:

58841

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

0.20

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T;.;T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.23

T;T;T;.;T;.

MetaRNN

Benign

0.0000047

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.94

.;L;L;L;L;.

PhyloP100

0.65

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.3

N;.;N;N;N;.

REVEL

Benign

0.061

Sift

Uncertain

0.024

D;.;D;D;D;.

Sift4G

Benign

0.14

T;T;T;T;T;T

Vest4

0.056

MutPred

0.27

Loss of methylation at K121 (P = 0.0613);Loss of methylation at K121 (P = 0.0613);Loss of methylation at K121 (P = 0.0613);Loss of methylation at K121 (P = 0.0613);Loss of methylation at K121 (P = 0.0613);Loss of methylation at K121 (P = 0.0613);

MPC

0.40

ClinPred

0.0087

GERP RS

1.3

Varity_R

0.14

gMVP

0.25

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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