dbSNP rs201748259: APOBEC3D:p.Phe83Tyr (chr22-39025107-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152426.4(APOBEC3D):c.248T>A(p.Phe83Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. F83C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63

Variant links:

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]

APOBEC3D links:

ENSG00000284554 (HGNC:):

ENSG00000284554 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3D	NM_152426.4 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 6		XP_016884085.1
APOBEC3D	XM_047441142.1 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 5		XP_047297098.1
APOBEC3D	NM_001363781.1 link	c.210+2093T>A		intron_variant	Intron 2 of 3		NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3D	ENST00000216099.13 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.210+2093T>A		intron_variant	Intron 2 of 3	1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.17+3571T>A		intron_variant	Intron 1 of 3	5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1448208

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.089

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.72

T;.

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.4

.;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

.;D

Vest4

0.51

MutPred

0.92

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.17

MPC

0.35

ClinPred

0.83

GERP RS

2.3

Varity_R

0.45

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over