22-39101399-G-C

Variant names:

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

Variant summary

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

The NM_001166003.3(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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G105V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.56 (25134 hom., cov: 22)
  • Exomes 𝑓: 0.47 (162677 hom.)
• Consequence: APOBEC3H NM_001166003.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 68 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=1.6928052E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166003.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	NM_181773.5	MANE Select	c.313G>C	p.Gly105Arg	missense	Exon 3 of 5	NP_861438.3
	APOBEC3H	NM_001166003.3		c.313G>C	p.Gly105Arg	missense	Exon 3 of 6	NP_001159475.2
	APOBEC3H	NM_001166002.3		c.313G>C	p.Gly105Arg	missense	Exon 3 of 5	NP_001159474.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	ENST00000442487.8	TSL:3 MANE Select	c.313G>C	p.Gly105Arg	missense	Exon 3 of 5	ENSP00000411754.3
	APOBEC3H	ENST00000348946.8	TSL:1	c.313G>C	p.Gly105Arg	missense	Exon 3 of 5	ENSP00000216123.5
	APOBEC3H	ENST00000613996.1	TSL:1	c.313G>C	p.Gly105Arg	missense	Exon 2 of 3	ENSP00000482682.1

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

GnomAD2 exomes AF: 0.470 AC: 117985 AN: 251172 AF XY: 0.470

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 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

African (AFR) AF: 0.829 AC: 27743 AN: 33478

American (AMR) AF: 0.353 AC: 15804 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 11915 AN: 26136

East Asian (EAS) AF: 0.318 AC: 12640 AN: 39700

South Asian (SAS) AF: 0.488 AC: 42111 AN: 86254

European-Finnish (FIN) AF: 0.544 AC: 29056 AN: 53398

Middle Eastern (MID) AF: 0.493 AC: 2825 AN: 5736

European-Non Finnish (NFE) AF: 0.459 AC: 509882 AN: 1111926

Other (OTH) AF: 0.470 AC: 28364 AN: 60390

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

African (AFR) AF: 0.816 AC: 33100 AN: 40544

American (AMR) AF: 0.417 AC: 6217 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1566 AN: 3440

East Asian (EAS) AF: 0.335 AC: 1662 AN: 4964

South Asian (SAS) AF: 0.475 AC: 2215 AN: 4660

European-Finnish (FIN) AF: 0.541 AC: 5512 AN: 10184

Middle Eastern (MID) AF: 0.479 AC: 137 AN: 286

European-Non Finnish (NFE) AF: 0.465 AC: 31207 AN: 67042

Other (OTH) AF: 0.498 AC: 1025 AN: 2060

Alfa AF: 0.335 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 v4.9

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
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.052	T
MetaRNN	Benign	0.0000017	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.6	N
PhyloP100		-1.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.068
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.051
MPC		0.22
ClinPred		0.0081	T
GERP RS		-4.6
Varity_R		0.13
gMVP		0.13
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: rs139297; hg19: chr22-39497404; COSMIC: COSV62378437; COSMIC: COSV62378437;