NM_181773.5:c.534G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 46 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: Likely_benign. The variant received -2 ACMG points.

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

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.534G>T	p.Glu178Asp	missense	Exon 4 of 5	NP_861438.3
	APOBEC3H	NM_001166003.3		c.534G>T	p.Glu178Asp	missense	Exon 4 of 6	NP_001159475.2
	APOBEC3H	NM_001166002.3		c.534G>T	p.Glu178Asp	missense	Exon 4 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.534G>T	p.Glu178Asp	missense	Exon 4 of 5	ENSP00000411754.3
	APOBEC3H	ENST00000348946.8	TSL:1	c.534G>T	p.Glu178Asp	missense	Exon 4 of 5	ENSP00000216123.5
	APOBEC3H	ENST00000613996.1	TSL:1	c.419-479G>T		intron	N/A	ENSP00000482682.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 12863

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.59	N
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.041
Sift	Benign	0.33	T
Sift4G	Benign	0.62	T
Vest4		0.036
MutPred		0.30		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
Mutation Taster		=100/0	polymorphism

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: rs139302; hg19: chr22-39498038;