Genetic Variant NM_152426.4:c.235G>A (chr22-39025094-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.235G>A	p.Ala79Thr	missense	Exon 3 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.210+2080G>A		intron	N/A	NP_001350710.1	Q6ICH2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3D	ENST00000216099.13	TSL:2 MANE Select	c.235G>A	p.Ala79Thr	missense	Exon 3 of 7	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9	TSL:1	c.235G>A	p.Ala79Thr	missense	Exon 3 of 7	ENSP00000370980.4
APOBEC3D	ENST00000427494.6	TSL:1	c.210+2080G>A		intron	N/A	ENSP00000388017.2	Q6ICH2

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

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

241788

AF XY:

0.0000153

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 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

African (AFR)

AF:

0.00

AC:

AN:

30056

American (AMR)

AF:

0.0000246

AC:

AN:

40656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20780

East Asian (EAS)

AF:

0.00

AC:

AN:

29312

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43520

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5076

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1031492

Other (OTH)

AF:

0.0000191

AC:

AN:

52398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000339

AC:

AN:

147604

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

71742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40250

American (AMR)

AF:

0.0000689

AC:

AN:

14514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

4866

South Asian (SAS)

AF:

0.00

AC:

AN:

4532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000596

AC:

AN:

67062

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0000734

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.64

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

2.0

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.32

Sift

Uncertain

0.014

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.27

MutPred

0.85

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

Mutation Taster

=93/7

polymorphism

(source)

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

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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