22-39100407-G-C

Variant names:

• chr22-39100407-G-C
• rs139294
• NM_181773.5:c.129G>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.129G>C​(p.Thr43Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,354 control chromosomes in the GnomAD database, including 182,444 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23864 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158580 hom.)
• Consequence: APOBEC3H NM_181773.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 21 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 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.129G>C	p.Thr43Thr	synonymous	Exon 2 of 5	NP_861438.3
	APOBEC3H	NM_001166003.3		c.129G>C	p.Thr43Thr	synonymous	Exon 2 of 6	NP_001159475.2
	APOBEC3H	NM_001166002.3		c.129G>C	p.Thr43Thr	synonymous	Exon 2 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.129G>C	p.Thr43Thr	synonymous	Exon 2 of 5	ENSP00000411754.3
	APOBEC3H	ENST00000348946.8	TSL:1	c.129G>C	p.Thr43Thr	synonymous	Exon 2 of 5	ENSP00000216123.5
	APOBEC3H	ENST00000613996.1	TSL:1	c.129G>C	p.Thr43Thr	synonymous	Exon 1 of 3	ENSP00000482682.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82290 AN: 151996 Hom.: 23829 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.465 AC: 116827 AN: 251086 AF XY: 0.466

Gnomad AFR exome AF: 0.772

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.460 AC: 672852 AN: 1461240 Hom.: 158580 Cov.: 58 AF XY: 0.461 AC XY: 335186 AN XY: 726850

African (AFR) AF: 0.783 AC: 26222 AN: 33468

American (AMR) AF: 0.348 AC: 15562 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11935 AN: 26130

East Asian (EAS) AF: 0.346 AC: 13746 AN: 39672

South Asian (SAS) AF: 0.490 AC: 42278 AN: 86222

European-Finnish (FIN) AF: 0.537 AC: 28691 AN: 53386

Middle Eastern (MID) AF: 0.488 AC: 2757 AN: 5654

European-Non Finnish (NFE) AF: 0.453 AC: 503654 AN: 1111652

Other (OTH) AF: 0.464 AC: 28007 AN: 60354

GnomAD4 genome AF: 0.542 AC: 82382 AN: 152114 Hom.: 23864 Cov.: 32 AF XY: 0.540 AC XY: 40160 AN XY: 74368

African (AFR) AF: 0.768 AC: 31861 AN: 41498

American (AMR) AF: 0.409 AC: 6242 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1576 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5178

South Asian (SAS) AF: 0.481 AC: 2320 AN: 4824

European-Finnish (FIN) AF: 0.531 AC: 5614 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31269 AN: 67988

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.445 Hom.: 4563

Bravo AF: 0.538

Asia WGS AF: 0.407 AC: 1421 AN: 3478

EpiCase AF: 0.453

EpiControl AF: 0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.52
PhyloP100		0.32
PromoterAI		-0.15	Neutral
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: rs139294; hg19: chr22-39496412; COSMIC: COSV62378673;