Variant chr22-39025218-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152426.4(APOBEC3D):c.359T>C(p.Leu120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,613,846 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: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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/exons	MANE	Protein	UniProt
APOBEC3D	NM_152426.4 link	c.359T>C	p.Leu120Ser	missense_variant	3/7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.359T>C	p.Leu120Ser	missense_variant	3/6		XP_016884085.1
APOBEC3D	XM_047441142.1 link	c.359T>C	p.Leu120Ser	missense_variant	3/5		XP_047297098.1
APOBEC3D	NM_001363781.1 link	c.210+2204T>C		intron_variant			NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3D	ENST00000216099.13 link	c.359T>C	p.Leu120Ser	missense_variant	3/7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.359T>C	p.Leu120Ser	missense_variant	3/7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.210+2204T>C		intron_variant		1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.17+3682T>C		intron_variant		5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251414

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135898

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000194

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.359T>C (p.L120S) alteration is located in exon 3 (coding exon 3) of the APOBEC3D gene. This alteration results from a T to C substitution at nucleotide position 359, causing the leucine (L) at amino acid position 120 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

0.18

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.70

T;.

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

3.9

.;H

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.80

MVP

0.63

MPC

0.38

ClinPred

0.95

GERP RS

2.3

Varity_R

0.37

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over