22-39022859-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 15/21 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

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
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]

Genome browser will be placed here

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=0.00765121).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBEC3DNM_152426.4 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 7 ENST00000216099.13 NP_689639.2 B2CML4
APOBEC3DNM_001363781.1 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 4 NP_001350710.1
APOBEC3DXM_017028596.3 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 6 XP_016884085.1
APOBEC3DXM_047441142.1 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 5 XP_047297098.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBEC3DENST00000216099.13 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 7 2 NM_152426.4 ENSP00000216099.7 Q96AK3
ENSG00000284554ENST00000381568.9 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 7 1 ENSP00000370980.4
APOBEC3DENST00000427494.6 linkc.55G>A p.Asp19Asn missense_variant Exon 2 of 4 1 ENSP00000388017.2 Q6ICH2
APOBEC3DENST00000622217.3 linkc.17+1323G>A intron_variant Intron 1 of 3 5 ENSP00000480718.3 A0A087WX48

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152112
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000924
AC:
23
AN:
249010
Hom.:
0
AF XY:
0.0000816
AC XY:
11
AN XY:
134776
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 SAS exome
AF:
0.0000658
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1459438
Hom.:
0
Cov.:
31
AF XY:
0.0000386
AC XY:
28
AN XY:
726050
show subpopulations
Gnomad4 AFR exome
AF:
0.000210
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000907
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 30, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.55G>A (p.D19N) alteration is located in exon 2 (coding exon 2) of the APOBEC3D gene. This alteration results from a G to A substitution at nucleotide position 55, causing the aspartic acid (D) at amino acid position 19 to be replaced by an asparagine (N). 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
0.12
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
3.5
DANN
Benign
0.76
DEOGEN2
Benign
0.021
.;.;T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0019
N
LIST_S2
Benign
0.43
T;T;.
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.0077
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
.;.;L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.39
N;N;N
REVEL
Benign
0.078
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.23
T;T;T
Polyphen
0.36, 0.0
.;B;B
Vest4
0.089
MVP
0.061
MPC
1.6
ClinPred
0.0047
T
GERP RS
-2.5
Varity_R
0.023
gMVP
0.73

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

LitVar

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

Other links and lift over

dbSNP: rs371353731; hg19: chr22-39418864; API