rs139302

Positions:

• chr22-39102033-G-C
• chr22-39102033-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181773.5(APOBEC3H):​c.534G>C​(p.Glu178Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,610,556 control chromosomes in the GnomAD database, including 186,293 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.55 (24656 hom., cov: 29)
  • Exomes 𝑓: 0.46 (161637 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=8.9006903E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.534G>C	p.Glu178Asp	missense_variant	4/5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.534G>C	p.Glu178Asp	missense_variant	4/5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83242 AN: 151702 Hom.: 24626 Cov.: 29

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.493

GnomAD3 exomes AF: 0.465 AC: 114404 AN: 246284 Hom.: 28678 AF XY: 0.466 AC XY: 62080 AN XY: 133134

Gnomad AFR exome AF: 0.799

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.339

Gnomad SAS exome AF: 0.487

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.464 AC: 677249 AN: 1458734 Hom.: 161637 Cov.: 54 AF XY: 0.465 AC XY: 337182 AN XY: 725518

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.549 AC: 83327 AN: 151822 Hom.: 24656 Cov.: 29 AF XY: 0.546 AC XY: 40547 AN XY: 74198

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.488

Alfa AF: 0.468 Hom.: 12863

Bravo AF: 0.544

TwinsUK AF: 0.461 AC: 1711

ALSPAC AF: 0.456 AC: 1756

ESP6500AA AF: 0.786 AC: 3461

ESP6500EA AF: 0.461 AC: 3964

ExAC AF: 0.477 AC: 57868

Asia WGS AF: 0.407 AC: 1417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.080
DANN	Benign	0.46
DEOGEN2	Benign	0.011	T;.;T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.27	T;T;.;T
MetaRNN	Benign	8.9e-7	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	.;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.33	.;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Vest4		0.036
MutPred		0.30		Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);
MPC		0.17
ClinPred		0.0085	T
GERP RS		-6.1
Varity_R		0.062
gMVP		0.36

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: rs139302; hg19: chr22-39498038; COSMIC: COSV62378740; COSMIC: COSV62378740;