chr22-39025224-A-G

Position:

• chr22-39025224-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152426.4(APOBEC3D):​c.365A>G​(p.Glu122Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOBEC3D NM_152426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.95

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]

ENSG00000284554 (HGNC:):

ACMG classification

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=0.16629025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3D	NM_152426.4	c.365A>G	p.Glu122Gly	missense_variant	3/7	ENST00000216099.13	NP_689639.2
APOBEC3D	XM_017028596.3	c.365A>G	p.Glu122Gly	missense_variant	3/6		XP_016884085.1
APOBEC3D	XM_047441142.1	c.365A>G	p.Glu122Gly	missense_variant	3/5		XP_047297098.1
APOBEC3D	NM_001363781.1	c.210+2210A>G		intron_variant			NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3D	ENST00000216099.13	c.365A>G	p.Glu122Gly	missense_variant	3/7	2	NM_152426.4	ENSP00000216099.7
ENSG00000284554	ENST00000381568.9	c.365A>G	p.Glu122Gly	missense_variant	3/7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6	c.210+2210A>G		intron_variant		1		ENSP00000388017.2
APOBEC3D	ENST00000622217.3	c.17+3688A>G		intron_variant		5		ENSP00000480718.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.365A>G (p.E122G) alteration is located in exon 3 (coding exon 3) of the APOBEC3D gene. This alteration results from a A to G substitution at nucleotide position 365, causing the glutamic acid (E) at amino acid position 122 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.6
DANN	Benign	0.80
DEOGEN2	Benign	0.13	.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.12
Sift	Benign	0.082	T;T
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	.;D
Vest4		0.16
MutPred		0.43		Loss of stability (P = 0.0598);Loss of stability (P = 0.0598);
MVP		0.34
MPC		0.34
ClinPred		0.41	T
GERP RS		-4.5
Varity_R		0.10
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39421229;