22-39100331-G-T

Variant names:

• chr22-39100331-G-T
• rs139293
• NM_181773.5:c.53G>T

Variant summary

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

The NM_181773.5(APOBEC3H):​c.53G>T​(p.Arg18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,612,954 control chromosomes in the GnomAD database, including 61,402 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 0.23 (4513 hom., cov: 31)
  • Exomes 𝑓: 0.27 (56889 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 43 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=0.005291611).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.53G>T	p.Arg18Leu	missense_variant	Exon 2 of 5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.53G>T	p.Arg18Leu	missense_variant	Exon 2 of 5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34298 AN: 151816 Hom.: 4511 Cov.: 31

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.268 AC: 67324 AN: 251224 AF XY: 0.279

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.274 AC: 399780 AN: 1461020 Hom.: 56889 Cov.: 40 AF XY: 0.277 AC XY: 201362 AN XY: 726738

African (AFR) AF: 0.0764 AC: 2559 AN: 33478

American (AMR) AF: 0.224 AC: 9989 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6932 AN: 26126

East Asian (EAS) AF: 0.143 AC: 5673 AN: 39694

South Asian (SAS) AF: 0.346 AC: 29780 AN: 86182

European-Finnish (FIN) AF: 0.376 AC: 20075 AN: 53390

Middle Eastern (MID) AF: 0.270 AC: 1556 AN: 5760

European-Non Finnish (NFE) AF: 0.277 AC: 307684 AN: 1111340

Other (OTH) AF: 0.257 AC: 15532 AN: 60362

GnomAD4 genome AF: 0.226 AC: 34304 AN: 151934 Hom.: 4513 Cov.: 31 AF XY: 0.231 AC XY: 17115 AN XY: 74236

African (AFR) AF: 0.0856 AC: 3551 AN: 41478

American (AMR) AF: 0.227 AC: 3468 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3468

East Asian (EAS) AF: 0.161 AC: 828 AN: 5152

South Asian (SAS) AF: 0.332 AC: 1596 AN: 4812

European-Finnish (FIN) AF: 0.375 AC: 3943 AN: 10514

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19168 AN: 67950

Other (OTH) AF: 0.207 AC: 436 AN: 2106

Alfa AF: 0.253 Hom.: 3823

Bravo AF: 0.205

TwinsUK AF: 0.268 AC: 992

ALSPAC AF: 0.273 AC: 1053

ESP6500AA AF: 0.0828 AC: 365

ESP6500EA AF: 0.274 AC: 2353

ExAC AF: 0.268 AC: 32578

Asia WGS AF: 0.222 AC: 775 AN: 3478

EpiCase AF: 0.273

EpiControl AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	.;T;.;T;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.49	T;T;T;.;T;.
MetaRNN	Benign	0.0053	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;L;L;L;.
PhyloP100		-0.12
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N;.;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.14	T;.;T;T;T;.
Sift4G	Uncertain	0.031	D;D;D;D;D;D
Vest4		0.18
MPC		0.47
ClinPred		0.012	T
GERP RS		-0.21
PromoterAI		-0.15	Neutral
Varity_R		0.25
gMVP		0.37
Mutation Taster		=96/4	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: rs139293; hg19: chr22-39496336; COSMIC: COSV62378623;