chr22-39100407-G-C

Position:

• chr22-39100407-G-C

Variant summary

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

The NM_181773.5(APOBEC3H):​c.129G>C​(p.Thr43=) 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

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.129G>C	p.Thr43=	synonymous_variant	2/5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.129G>C	p.Thr43=	synonymous_variant	2/5	3	NM_181773.5	ENSP00000411754	A2

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

GnomAD3 exomes AF: 0.465 AC: 116827 AN: 251086 Hom.: 28562 AF XY: 0.466 AC XY: 63333 AN XY: 135784

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 SAS exome AF: 0.489

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

Gnomad4 AFR exome AF: 0.783

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.464

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

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.487

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.52

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: rs139294; hg19: chr22-39496412; COSMIC: COSV62378673;