rs139299

chr22-39101449-G-Cchr22-39101449-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.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. 13/19 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. K121E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.56 (25222 hom., cov: 21)
  • Exomes 𝑓: 0.47 (165681 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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=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/exons	MANE	UniProt
APOBEC3H	NM_181773.5	c.363G>C	p.Lys121Asn	missense_variant	3/5	ENST00000442487.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.363G>C	p.Lys121Asn	missense_variant	3/5	3	NM_181773.5	A2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 83144 AN: 148366 Hom.: 25185 Cov.: 21

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

GnomAD3 exomes AF: 0.474 AC: 118872 AN: 250840 Hom.: 29816 AF XY: 0.475 AC XY: 64379 AN XY: 135648

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 SAS exome AF: 0.492

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.: 57 AF XY: 0.470 AC XY: 341879 AN XY: 726932

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: 0.561 AC: 83237 AN: 148484 Hom.: 25222 Cov.: 21 AF XY: 0.559 AC XY: 40382 AN XY: 72258

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.500

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	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	12
Dann	Uncertain	0.99
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.23	T;T;T;.;T;.
MetaRNN	Benign	0.0000047	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.26	T
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	T
GERP RS		1.3
Varity_R		0.14
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs139299; hg19: chr22-39497454; COSMIC: COSV62378445; COSMIC: COSV62378445;