rs139292

Positions:

• chr22-39100317-TAAC-T
• chr22-39100317-TAAC-TAACAAC

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PM4_Supporting BA1

The NM_181773.5(APOBEC3H):​c.45_47del​(p.Asn15del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,612,182 control chromosomes in the GnomAD database, including 91,344 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8404 hom., cov: 0)
  • Exomes 𝑓: 0.33 (82940 hom.)
• Consequence: APOBEC3H NM_181773.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_181773.5. Strenght limited to Supporting due to length of the change: 1aa.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC3H	NM_181773.5	c.45_47del	p.Asn15del	inframe_deletion	2/5	ENST00000442487.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.45_47del	p.Asn15del	inframe_deletion	2/5	3	NM_181773.5	A2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50235 AN: 151596 Hom.: 8393 Cov.: 0

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.338 AC: 84816 AN: 251022 Hom.: 14787 AF XY: 0.347 AC XY: 47096 AN XY: 135694

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.440

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.334 AC: 487150 AN: 1460470 Hom.: 82940 AF XY: 0.338 AC XY: 245352 AN XY: 726438

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.331 AC: 50282 AN: 151712 Hom.: 8404 Cov.: 0 AF XY: 0.335 AC XY: 24823 AN XY: 74126

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.296

Alfa AF: 0.330 Hom.: 1522

Bravo AF: 0.316

Asia WGS AF: 0.322 AC: 1127 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs139292; hg19: chr22-39496322;