NM_181773.5:c.49C>T

Variant names:

• chr22-39100327-C-T
• rs374766186
• NM_181773.5:c.49C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181773.5(APOBEC3H):​c.49C>T​(p.Arg17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: APOBEC3H NM_181773.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.276
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2106595).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	NM_181773.5	MANE Select	c.49C>T	p.Arg17Cys	missense	Exon 2 of 5	NP_861438.3	B7TQM3
	APOBEC3H	NM_001166003.3		c.49C>T	p.Arg17Cys	missense	Exon 2 of 6	NP_001159475.2	Q6NTF7-1
	APOBEC3H	NM_001166002.3		c.49C>T	p.Arg17Cys	missense	Exon 2 of 5	NP_001159474.2	B7TQM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3H	ENST00000442487.8	TSL:3 MANE Select	c.49C>T	p.Arg17Cys	missense	Exon 2 of 5	ENSP00000411754.3	Q6NTF7-3
	APOBEC3H	ENST00000348946.8	TSL:1	c.49C>T	p.Arg17Cys	missense	Exon 2 of 5	ENSP00000216123.5	Q6NTF7-2
	APOBEC3H	ENST00000613996.1	TSL:1	c.49C>T	p.Arg17Cys	missense	Exon 1 of 3	ENSP00000482682.1	A0A087WZI3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251430 AF XY: 0.0000368

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000588 AC: 86 AN: 1461796 Hom.: 0 Cov.: 40 AF XY: 0.0000591 AC XY: 43 AN XY: 727188

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111934

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74266

African (AFR) AF: 0.0000242 AC: 1 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.28
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.21
Sift	Benign	0.14	T
Sift4G	Uncertain	0.033	D
Vest4		0.20
MVP		0.32
MPC		0.60
ClinPred		0.10	T
GERP RS		1.9
PromoterAI		-0.12	Neutral
Varity_R		0.31
gMVP		0.21
Mutation Taster		=95/5	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: rs374766186; hg19: chr22-39496332; COSMIC: COSV62378692;