Genetic Variant APOBEC3D:p.Asp19Asn (chr22-39022859-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152426.4(APOBEC3D):c.55G>A(p.Asp19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Publications

3 publications found

Variant links:

Genes affected

APOBEC3D (HGNC:17354): (apolipoprotein B mRNA editing enzyme catalytic subunit 3D) This gene is a member of the cytidine deaminase gene family. It is one of a group of related genes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1 and inhibit retroviruses, such as HIV, by deaminating cytosine residues in nascent retroviral cDNA. [provided by RefSeq, Jul 2008]

APOBEC3D links:

ENSG00000284554 (HGNC:):

ENSG00000284554 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00765121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152426.4. 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
	APOBEC3D	NM_152426.4	MANE Select	c.55G>A	p.Asp19Asn	missense	Exon 2 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.55G>A	p.Asp19Asn	missense	Exon 2 of 4	NP_001350710.1	Q6ICH2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3D	ENST00000216099.13	TSL:2 MANE Select	c.55G>A	p.Asp19Asn	missense	Exon 2 of 7	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9	TSL:1	c.55G>A	p.Asp19Asn	missense	Exon 2 of 7	ENSP00000370980.4
APOBEC3D	ENST00000427494.6	TSL:1	c.55G>A	p.Asp19Asn	missense	Exon 2 of 4	ENSP00000388017.2	Q6ICH2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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

GnomAD2 exomes

AF:

0.0000924

AC:

AN:

249010

AF XY:

0.0000816

show subpopulations

Gnomad AFR exome

AF:

0.000561

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1459438

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

726050

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33358

American (AMR)

AF:

0.0000225

AC:

AN:

44472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.000907

AC:

AN:

39672

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4724

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111480

Other (OTH)

AF:

0.0000166

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41536

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.5

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.021

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.43

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-1.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.39

REVEL

Benign

0.078

Sift

Benign

1.0

Sift4G

Benign

0.23

Polyphen

0.36

Vest4

0.089

MVP

0.061

MPC

1.6

ClinPred

0.0047

GERP RS

-2.5

Varity_R

0.023

gMVP

0.73

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over