22-39029380-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152426.4(APOBEC3D):​c.623T>C​(p.Met208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

APOBEC3D
NM_152426.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.202
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20588866).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBEC3DNM_152426.4 linkc.623T>C p.Met208Thr missense_variant Exon 5 of 7 ENST00000216099.13 NP_689639.2 B2CML4
APOBEC3DXM_017028596.3 linkc.830T>C p.Met277Thr missense_variant Exon 4 of 6 XP_016884085.1
APOBEC3DNM_001363781.1 linkc.211-2314T>C intron_variant Intron 2 of 3 NP_001350710.1
APOBEC3DXM_047441142.1 linkc.606-2314T>C intron_variant Intron 4 of 4 XP_047297098.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBEC3DENST00000216099.13 linkc.623T>C p.Met208Thr missense_variant Exon 5 of 7 2 NM_152426.4 ENSP00000216099.7 Q96AK3
ENSG00000284554ENST00000381568.9 linkc.623T>C p.Met208Thr missense_variant Exon 5 of 7 1 ENSP00000370980.4
APOBEC3DENST00000427494.6 linkc.211-2314T>C intron_variant Intron 2 of 3 1 ENSP00000388017.2 Q6ICH2
APOBEC3DENST00000622217.3 linkc.35T>C p.Met12Thr missense_variant Exon 2 of 4 5 ENSP00000480718.3 A0A087WX48

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251426
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.623T>C (p.M208T) alteration is located in exon 5 (coding exon 5) of the APOBEC3D gene. This alteration results from a T to C substitution at nucleotide position 623, causing the methionine (M) at amino acid position 208 to be replaced by a threonine (T). 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
Benign
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
1.9
DANN
Benign
0.29
DEOGEN2
Benign
0.050
.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.46
T;.;T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.3
.;M;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.8
N;N;.
REVEL
Benign
0.12
Sift
Benign
0.21
T;T;.
Sift4G
Benign
0.20
T;T;T
Polyphen
0.0010
.;B;.
Vest4
0.11
MutPred
0.76
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP
0.081
MPC
0.055
ClinPred
0.035
T
GERP RS
0.80
Varity_R
0.054
gMVP
0.44

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.

Other links and lift over

dbSNP: rs780647042; hg19: chr22-39425385; API