Variant 22-39025112-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152426.4(APOBEC3D):c.253T>C(p.Ser85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.824

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3D	NM_152426.4 link	c.253T>C	p.Ser85Pro	missense_variant	3/7	ENST00000216099.13	NP_689639.2	B2CML4
APOBEC3D	XM_017028596.3 link	c.253T>C	p.Ser85Pro	missense_variant	3/6		XP_016884085.1
APOBEC3D	XM_047441142.1 link	c.253T>C	p.Ser85Pro	missense_variant	3/5		XP_047297098.1
APOBEC3D	NM_001363781.1 link	c.210+2098T>C		intron_variant			NP_001350710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3D	ENST00000216099.13 link	c.253T>C	p.Ser85Pro	missense_variant	3/7	2	NM_152426.4	ENSP00000216099.7	Q96AK3
ENSG00000284554	ENST00000381568.9 link	c.253T>C	p.Ser85Pro	missense_variant	3/7	1		ENSP00000370980.4
APOBEC3D	ENST00000427494.6 link	c.210+2098T>C		intron_variant		1		ENSP00000388017.2	Q6ICH2
APOBEC3D	ENST00000622217.3 link	c.17+3576T>C		intron_variant		5		ENSP00000480718.3	A0A087WX48

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248734

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134474

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:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458404

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725136

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

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

Nov 21, 2024

The c.253T>C (p.S85P) 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 253, causing the serine (S) at amino acid position 85 to be replaced by a proline (P). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.78

T;.

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.25

Sift

Benign

0.14

T;T

Sift4G

Benign

0.15

T;T

Polyphen

1.0

.;D

Vest4

0.48

MutPred

0.68

Gain of catalytic residue at W86 (P = 0.0738);Gain of catalytic residue at W86 (P = 0.0738);

MVP

0.40

MPC

0.33

ClinPred

0.18

GERP RS

-1.7

Varity_R

0.16

gMVP

0.73

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