22-39025292-T-C

Variant names:

• chr22-39025292-T-C
• rs779603257
• NM_152426.4:c.433T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152426.4(APOBEC3D):​c.433T>C​(p.Trp145Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W145C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOBEC3D NM_152426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016293794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3D	NM_152426.4	c.433T>C	p.Trp145Arg	missense_variant	Exon 3 of 7	ENST00000216099.13	NP_689639.2
APOBEC3D	XM_017028596.3	c.433T>C	p.Trp145Arg	missense_variant	Exon 3 of 6		XP_016884085.1
APOBEC3D	XM_047441142.1	c.433T>C	p.Trp145Arg	missense_variant	Exon 3 of 5		XP_047297098.1
APOBEC3D	NM_001363781.1	c.210+2278T>C		intron_variant	Intron 2 of 3		NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3D	ENST00000216099.13	c.433T>C	p.Trp145Arg	missense_variant	Exon 3 of 7	2	NM_152426.4	ENSP00000216099.7
ENSG00000284554	ENST00000381568.9	c.433T>C	p.Trp145Arg	missense_variant	Exon 3 of 7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6	c.210+2278T>C		intron_variant	Intron 2 of 3	1		ENSP00000388017.2
APOBEC3D	ENST00000622217.3	c.17+3756T>C		intron_variant	Intron 1 of 3	5		ENSP00000480718.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0030
DANN	Benign	0.22
DEOGEN2	Benign	0.016	.;T
Eigen	Benign	-2.9
Eigen_PC	Benign	-2.9
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.20	T;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	3.5	N;N
REVEL	Benign	0.044
Sift	Benign	0.52	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.0	.;B
Vest4		0.13
MutPred		0.42		Gain of methylation at R149 (P = 0.0432);Gain of methylation at R149 (P = 0.0432);
MVP		0.030
MPC		0.078
ClinPred		0.027	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.18

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

Other links and lift over

dbSNP: rs779603257; hg19: chr22-39421297;