chr22-39025637-G-A

Variant names:

• chr22-39025637-G-A
• NM_152426.4:c.571G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152426.4(APOBEC3D):​c.571G>A​(p.Ala191Thr) 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. 17/22 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: -1.38
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055232793).

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.571G>A	p.Ala191Thr	missense	Exon 4 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.210+2623G>A		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.571G>A	p.Ala191Thr	missense	Exon 4 of 7	ENSP00000216099.7	Q96AK3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.571G>A	p.Ala191Thr	missense	Exon 4 of 7	ENSP00000370980.4
	APOBEC3D	ENST00000427494.6	TSL:1	c.210+2623G>A		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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.10
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.14
Sift	Benign	0.66	T
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.11
MutPred		0.31		Loss of helix (P = 0.1299)
MVP		0.17
MPC		0.22
ClinPred		0.11	T
GERP RS		-4.9
Varity_R		0.017
gMVP		0.073
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr22-39421642;