NM_152426.4:c.509A>C

Variant names:

• chr22-39025575-A-C
• NM_152426.4:c.509A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152426.4(APOBEC3D):​c.509A>C​(p.Glu170Ala) 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. 15/22 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: 1.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11278033).

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.509A>C	p.Glu170Ala	missense	Exon 4 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.210+2561A>C		intron	N/A	NP_001350710.1	Q6ICH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3D	ENST00000216099.13	TSL:2 MANE Select	c.509A>C	p.Glu170Ala	missense	Exon 4 of 7	ENSP00000216099.7	Q96AK3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.509A>C	p.Glu170Ala	missense	Exon 4 of 7	ENSP00000370980.4
	APOBEC3D	ENST00000427494.6	TSL:1	c.210+2561A>C		intron	N/A	ENSP00000388017.2	Q6ICH2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.076
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.024	D
Polyphen		0.12	B
Vest4		0.15
MutPred		0.49		Loss of loop (P = 0.2237)
MVP		0.24
MPC		0.093
ClinPred		0.25	T
GERP RS		1.4
Varity_R		0.15
gMVP		0.31
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr22-39421580;