22-39101399-G-C

Variant names:

• chr22-39101399-G-C
• rs139297
• NM_181773.5:c.313G>C

Variant summary

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

The NM_181773.5(APOBEC3H):​c.313G>C​(p.Gly105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,610,706 control chromosomes in the GnomAD database, including 187,811 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 0.56 (25134 hom., cov: 22)
  • Exomes 𝑓: 0.47 (162677 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=1.6928052E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.313G>C	p.Gly105Arg	missense_variant	Exon 3 of 5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.313G>C	p.Gly105Arg	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 83026 AN: 148862 Hom.: 25099 Cov.: 22

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.470 AC: 117985 AN: 251172 Hom.: 29398 AF XY: 0.470 AC XY: 63853 AN XY: 135800

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.487

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.465 AC: 680340 AN: 1461740 Hom.: 162677 Cov.: 64 AF XY: 0.466 AC XY: 338653 AN XY: 727180

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.558 AC: 83112 AN: 148966 Hom.: 25134 Cov.: 22 AF XY: 0.556 AC XY: 40337 AN XY: 72512

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.498

Alfa AF: 0.436 Hom.: 4607

Bravo AF: 0.554

TwinsUK AF: 0.461 AC: 1710

ALSPAC AF: 0.455 AC: 1755

ESP6500AA AF: 0.811 AC: 3573

ESP6500EA AF: 0.461 AC: 3964

ExAC AF: 0.481 AC: 58450

Asia WGS AF: 0.388 AC: 1275 AN: 3278

EpiCase AF: 0.457

EpiControl AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0010
DANN	Benign	0.16
DEOGEN2	Benign	0.0027	.;T;.;T;.;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.052	T;T;T;.;T;.
MetaRNN	Benign	0.0000017	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.6	.;N;N;N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	3.4	N;.;N;N;N;.
REVEL	Benign	0.068
Sift	Benign	1.0	T;.;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Vest4		0.051
MPC		0.22
ClinPred		0.0081	T
GERP RS		-4.6
Varity_R		0.13
gMVP		0.13

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: rs139297; hg19: chr22-39497404; COSMIC: COSV62378437; COSMIC: COSV62378437;