dbSNP rs752483265: APOBEC3D:p.Ala79Thr (chr22-39025094-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152426.4(APOBEC3D):c.235G>A(p.Ala79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,484,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A79P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3D	NM_152426.4 link	c.235G>A	p.Ala79Thr	missense_variant	Exon 3 of 7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.235G>A	p.Ala79Thr	missense_variant	Exon 3 of 6		XP_016884085.1
APOBEC3D	XM_047441142.1 link	c.235G>A	p.Ala79Thr	missense_variant	Exon 3 of 5		XP_047297098.1
APOBEC3D	NM_001363781.1 link	c.210+2080G>A		intron_variant	Intron 2 of 3		NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3D	ENST00000216099.13 link	c.235G>A	p.Ala79Thr	missense_variant	Exon 3 of 7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.235G>A	p.Ala79Thr	missense_variant	Exon 3 of 7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.210+2080G>A		intron_variant	Intron 2 of 3	1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.17+3558G>A		intron_variant	Intron 1 of 3	5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

AF:

0.0000339

AC:

AN:

147604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000689

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:

0.0000596

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

241788

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000135

AC:

AN:

1336606

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

662480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000191

GnomAD4 genome

AF:

0.0000339

AC:

AN:

147604

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

71742

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000689

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000596

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000734

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.64

T;.

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

1.0

.;D

Vest4

0.27

MutPred

0.85

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);

MVP

0.55

MPC

0.18

ClinPred

0.32

GERP RS

1.2

Varity_R

0.070

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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