22-39102033-G-C

Variant names:

• chr22-39102033-G-C
• rs139302
• NM_181773.5:c.534G>C

Variant summary

Our verdict is Benign. The variant received -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. 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 0.55 (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
• Publications: 46 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=8.9006903E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	NM_181773.5	MANE Select	c.534G>C	p.Glu178Asp	missense	Exon 4 of 5	NP_861438.3
	APOBEC3H	NM_001166003.3		c.534G>C	p.Glu178Asp	missense	Exon 4 of 6	NP_001159475.2
	APOBEC3H	NM_001166002.3		c.534G>C	p.Glu178Asp	missense	Exon 4 of 5	NP_001159474.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	ENST00000442487.8	TSL:3 MANE Select	c.534G>C	p.Glu178Asp	missense	Exon 4 of 5	ENSP00000411754.3
	APOBEC3H	ENST00000348946.8	TSL:1	c.534G>C	p.Glu178Asp	missense	Exon 4 of 5	ENSP00000216123.5
	APOBEC3H	ENST00000613996.1	TSL:1	c.419-479G>C		intron	N/A	ENSP00000482682.1

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

GnomAD2 exomes AF: 0.465 AC: 114404 AN: 246284 AF XY: 0.466

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 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

African (AFR) AF: 0.806 AC: 26916 AN: 33390

American (AMR) AF: 0.322 AC: 14214 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11886 AN: 26022

East Asian (EAS) AF: 0.337 AC: 13283 AN: 39452

South Asian (SAS) AF: 0.487 AC: 41921 AN: 85994

European-Finnish (FIN) AF: 0.544 AC: 28850 AN: 53054

Middle Eastern (MID) AF: 0.493 AC: 2838 AN: 5762

European-Non Finnish (NFE) AF: 0.458 AC: 509174 AN: 1110584

Other (OTH) AF: 0.467 AC: 28167 AN: 60268

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

African (AFR) AF: 0.793 AC: 32794 AN: 41360

American (AMR) AF: 0.395 AC: 6033 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1826 AN: 5160

South Asian (SAS) AF: 0.475 AC: 2286 AN: 4810

European-Finnish (FIN) AF: 0.536 AC: 5660 AN: 10558

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31498 AN: 67898

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

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 v4.9

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
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.051
Sift	Benign	0.33	T
Sift4G	Benign	0.62	T
Vest4		0.036
MutPred		0.30		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
Mutation Taster		=100/0	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: rs139302; hg19: chr22-39498038; COSMIC: COSV62378740; COSMIC: COSV62378740;