rs139298

Positions:

• chr22-39101447-A-G

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K121N) has been classified as Likely benign.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.361A>G	p.Lys121Glu	missense_variant	3/5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.361A>G	p.Lys121Glu	missense_variant	3/5	3	NM_181773.5	ENSP00000411754	A2

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

GnomAD3 exomes AF: 0.474 AC: 118877 AN: 250842 Hom.: 29816 AF XY: 0.475 AC XY: 64381 AN XY: 135646

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 SAS exome AF: 0.493

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

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.475

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

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.500

Alfa AF: 0.483 Hom.: 38533

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	0.0034	.;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	-1.4	.;N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
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
MPC		0.26
ClinPred		0.0019	T
GERP RS		-6.7
Varity_R		0.063
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs139298; hg19: chr22-39497452; COSMIC: COSV62378442; COSMIC: COSV62378442;