rs752483265

Variant names:

• chr22-39025094-G-C
• rs752483265
• NM_152426.4:c.235G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-39025094-G-C
• chr22-39025094-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152426.4(APOBEC3D):​c.235G>C​(p.Ala79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,336,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: APOBEC3D NM_152426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

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.235G>C	p.Ala79Pro	missense	Exon 3 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.210+2080G>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.235G>C	p.Ala79Pro	missense	Exon 3 of 7	ENSP00000216099.7	Q96AK3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.235G>C	p.Ala79Pro	missense	Exon 3 of 7	ENSP00000370980.4
	APOBEC3D	ENST00000427494.6	TSL:1	c.210+2080G>C		intron	N/A	ENSP00000388017.2	Q6ICH2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 241788 AF XY: 0.0000230

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000434 AC: 58 AN: 1336608 Hom.: 0 Cov.: 35 AF XY: 0.0000423 AC XY: 28 AN XY: 662482

African (AFR) AF: 0.00 AC: 0 AN: 30056

American (AMR) AF: 0.00 AC: 0 AN: 40656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20780

East Asian (EAS) AF: 0.00 AC: 0 AN: 29312

South Asian (SAS) AF: 0.00 AC: 0 AN: 83316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5076

European-Non Finnish (NFE) AF: 0.0000562 AC: 58 AN: 1031494

Other (OTH) AF: 0.00 AC: 0 AN: 52398

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000367 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.29
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.9
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.54
Sift	Benign	0.39	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.89		Gain of loop (P = 0.0851)
MVP		0.50
MPC		0.37
ClinPred		0.17	T
GERP RS		1.2
Varity_R		0.24
gMVP		0.82
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

dbSNP: rs752483265; hg19: chr22-39421099;