Genetic Variant NM_181773.5:c.364G>A (chr22-39101450-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_181773.5(APOBEC3H):c.364G>A(p.Gly122Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,434 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: 21)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.46

Variant links:

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]

APOBEC3H links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3H	NM_181773.5 link	c.364G>A	p.Gly122Arg	missense_variant	Exon 3 of 5	ENST00000442487.8	NP_861438.3	Q6NTF7-3B7TQM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3H	ENST00000442487.8 link	c.364G>A	p.Gly122Arg	missense_variant	Exon 3 of 5	3	NM_181773.5	ENSP00000411754.3		Q6NTF7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250924

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.;T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.55

T;T;T;.;T;.

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Pathogenic

3.1

.;M;M;M;M;.

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.9

D;.;D;D;D;.

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;.;D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Vest4

0.68

MutPred

0.90

Gain of MoRF binding (P = 0.0421);Gain of MoRF binding (P = 0.0421);Gain of MoRF binding (P = 0.0421);Gain of MoRF binding (P = 0.0421);Gain of MoRF binding (P = 0.0421);Gain of MoRF binding (P = 0.0421);

MVP

0.53

MPC

0.81

ClinPred

0.90

GERP RS

3.3

Varity_R

0.72

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over