dbSNP rs778365707: APOBEC3D:p.Asn125Thr (chr22-39025233-A-C) – 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.374A>C(p.Asn125Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,762 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.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

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.374A>C	p.Asn125Thr	missense_variant	Exon 3 of 7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.374A>C	p.Asn125Thr	missense_variant	Exon 3 of 6		XP_016884085.1
APOBEC3D	XM_047441142.1 link	c.374A>C	p.Asn125Thr	missense_variant	Exon 3 of 5		XP_047297098.1
APOBEC3D	NM_001363781.1 link	c.210+2219A>C		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.374A>C	p.Asn125Thr	missense_variant	Exon 3 of 7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.374A>C	p.Asn125Thr	missense_variant	Exon 3 of 7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.210+2219A>C		intron_variant	Intron 2 of 3	1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.17+3697A>C		intron_variant	Intron 1 of 3	5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.81

T;.

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

3.0

.;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.028

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

1.0

.;D

Vest4

0.45

MutPred

0.67

Gain of glycosylation at N125 (P = 0.0545);Gain of glycosylation at N125 (P = 0.0545);

MVP

0.45

MPC

0.33

ClinPred

0.36

GERP RS

1.2

Varity_R

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over