Variant chr22-39101450-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181773.5(APOBEC3H):c.364G>T(p.Gly122Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 149,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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, 0.992

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC3H	NM_181773.5 linkuse as main transcript	c.364G>T	p.Gly122Trp	missense_variant	3/5	ENST00000442487.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC3H	ENST00000442487.8 linkuse as main transcript	c.364G>T	p.Gly122Trp	missense_variant	3/5	3	NM_181773.5	A2	Q6NTF7-3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000984

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250924

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727028

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149914

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73022

show subpopulations

Gnomad4 AFR

AF:

0.0000984

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.364G>T (p.G122W) alteration is located in exon 3 (coding exon 2) of the APOBEC3H gene. This alteration results from a G to T substitution at nucleotide position 364, causing the glycine (G) at amino acid position 122 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

0.0063

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T;.;T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.50

T;T;T;.;T;.

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Pathogenic

3.1

.;M;M;M;M;.

MutationTaster

Benign

0.66

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-7.1

D;.;D;D;D;.

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;.;D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Vest4

0.66

MutPred

0.87

Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);

MVP

0.42

MPC

0.81

ClinPred

0.95

GERP RS

3.3

Varity_R

0.72

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over