22-39101328-C-G

Variant names:

• chr22-39101328-C-G
• rs997573747
• NM_181773.5:c.242C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181773.5(APOBEC3H):​c.242C>G​(p.Thr81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.242C>G	p.Thr81Arg	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.242C>G	p.Thr81Arg	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T;.;T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.92	D;D;D;.;D;.
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D
MetaSVM	Uncertain	0.0061	D
MutationAssessor	Uncertain	2.5	.;M;M;M;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D;.;D;D;D;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D;.;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Vest4		0.57
MutPred		0.87		Gain of catalytic residue at T81 (P = 0.0995);Gain of catalytic residue at T81 (P = 0.0995);Gain of catalytic residue at T81 (P = 0.0995);Gain of catalytic residue at T81 (P = 0.0995);Gain of catalytic residue at T81 (P = 0.0995);Gain of catalytic residue at T81 (P = 0.0995);
MVP		0.093
MPC		0.79
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.87
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.56		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs997573747; hg19: chr22-39497333;