22-39102033-G-T

Variant names:

• chr22-39102033-G-T
• rs139302
• NM_181773.5:c.534G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181773.5(APOBEC3H):​c.534G>T​(p.Glu178Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 29)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03748995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5	c.534G>T	p.Glu178Asp	missense_variant	Exon 4 of 5	ENST00000442487.8	NP_861438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8	c.534G>T	p.Glu178Asp	missense_variant	Exon 4 of 5	3	NM_181773.5	ENSP00000411754.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.12
DANN	Benign	0.50
DEOGEN2	Benign	0.011	T;.;T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.27	T;T;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	.;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.33	.;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Vest4		0.036
MutPred		0.30		Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);Loss of methylation at K174 (P = 0.1316);
MVP		0.043
MPC		0.17
ClinPred		0.071	T
GERP RS		-6.1
Varity_R		0.062
gMVP		0.36

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: rs139302; hg19: chr22-39498038;