22-39101447-A-G

Variant names:

• chr22-39101447-A-G
• rs139298
• NM_181773.5:c.361A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 44 publications found

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]

ACMG classification

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	c.361A>G	p.Lys121Glu	missense_variant	Exon 3 of 5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.361A>G	p.Lys121Glu	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 83167 AN: 147912 Hom.: 25210 Cov.: 21

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

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.: 57 AF XY: 0.470 AC XY: 341894 AN XY: 726944

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

GnomAD4 genome AF: 0.562 AC: 83260 AN: 148032 Hom.: 25247 Cov.: 21 AF XY: 0.561 AC XY: 40398 AN XY: 72014

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

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	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0020
DANN	Benign	0.16
DEOGEN2	Benign	0.0	.;T;.;T;.;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.17	T;T;T;.;T;.
MetaRNN	Benign	0.0000031	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N;N;N;.
PhyloP100		-2.1
PrimateAI	Benign	0.25	T
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
ClinPred		0.0019	T
GERP RS		-6.7
Varity_R		0.063
gMVP		0.16
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: rs139298; hg19: chr22-39497452; COSMIC: COSV62378442; COSMIC: COSV62378442;