Variant chr22-39101282-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181773.5(APOBEC3H):c.196A>G(p.Met66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

APOBEC3H
NM_181773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.251

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC3H	NM_181773.5 linkuse as main transcript	c.196A>G	p.Met66Val	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.196A>G	p.Met66Val	missense_variant	3/5	3	NM_181773.5	A2	Q6NTF7-3

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

151436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.000965

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

251448

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000409

AC:

AN:

151436

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

AN XY:

73906

show subpopulations

Gnomad4 AFR

AF:

0.00143

Gnomad4 AMR

AF:

0.0000658

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:

0.000965

Alfa

AF:

0.0000800

Hom.:

Bravo

AF:

0.000472

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

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 27, 2022

The c.196A>G (p.M66V) alteration is located in exon 3 (coding exon 2) of the APOBEC3H gene. This alteration results from a A to G substitution at nucleotide position 196, causing the methionine (M) at amino acid position 66 to be replaced by a valine (V). 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

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.4

DANN

Benign

0.69

DEOGEN2

Benign

0.015

.;T;.;T;.;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.72

T;T;T;.;T;.

M_CAP

Benign

0.044

MetaRNN

Benign

0.021

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

.;L;L;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;.;N;N;N;.

REVEL

Benign

0.13

Sift

Benign

0.14

T;.;T;T;T;.

Sift4G

Benign

0.079

T;D;D;D;D;T

Vest4

0.17

MVP

0.043

MPC

0.53

ClinPred

0.039

GERP RS

-0.13

Varity_R

0.37

gMVP

0.14

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

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