Variant chr22-39029463-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152426.4(APOBEC3D):c.706G>C(p.Glu236Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 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: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12237203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3D	NM_152426.4 link	c.706G>C	p.Glu236Gln	missense_variant	5/7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.913G>C	p.Glu305Gln	missense_variant	4/6		XP_016884085.1
APOBEC3D	NM_001363781.1 link	c.211-2231G>C		intron_variant			NP_001350710.1
APOBEC3D	XM_047441142.1 link	c.606-2231G>C		intron_variant			XP_047297098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3D	ENST00000216099.13 link	c.706G>C	p.Glu236Gln	missense_variant	5/7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.706G>C	p.Glu236Gln	missense_variant	5/7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.211-2231G>C		intron_variant		1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.118G>C	p.Glu40Gln	missense_variant	2/4	5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000274

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

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

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

The c.706G>C (p.E236Q) alteration is located in exon 5 (coding exon 5) of the APOBEC3D gene. This alteration results from a G to C substitution at nucleotide position 706, causing the glutamic acid (E) at amino acid position 236 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.51

DANN

Benign

0.78

DEOGEN2

Benign

0.038

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.61

T;.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.076

Sift

Benign

0.031

D;D;.

Sift4G

Uncertain

0.055

T;T;D

Polyphen

0.38

.;B;.

Vest4

0.17

MutPred

0.62

Gain of MoRF binding (P = 0.0394);Gain of MoRF binding (P = 0.0394);.;

MVP

0.16

MPC

0.060

ClinPred

0.035

GERP RS

-2.5

Varity_R

0.070

gMVP

0.22

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over