22-38984140-A-G

Variant summary

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

The ENST00000333467.4(APOBEC3B):ā€‹c.83A>Gā€‹(p.Tyr28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,591,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000047 ( 1 hom., cov: 31)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

APOBEC3B
ENST00000333467.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12
Variant links:
Genes affected
APOBEC3B (HGNC:17352): (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes 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. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. A hybrid gene results from the deletion of approximately 29.5 kb of sequence between this gene, APOBEC3B, and the adjacent gene APOBEC3A. The breakpoints of the deletion are within the two genes, so the deletion allele is predicted to have the promoter and coding region of APOBEC3A, but the 3' UTR of APOBEC3B. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

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=0.11286616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APOBEC3BNM_004900.5 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant 2/8 ENST00000333467.4 NP_004891.5
APOBEC3BNM_001270411.2 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant 2/8 NP_001257340.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APOBEC3BENST00000333467.4 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant 2/81 NM_004900.5 ENSP00000327459 P2Q9UH17-1
APOBEC3BENST00000407298.7 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant 2/81 ENSP00000385068 Q9UH17-3
APOBEC3BENST00000335760.9 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant, NMD_transcript_variant 2/71 ENSP00000338897 Q9UH17-2
APOBEC3BENST00000402182.7 linkuse as main transcriptc.83A>G p.Tyr28Cys missense_variant 2/72 ENSP00000385060 A2

Frequencies

GnomAD3 genomes
AF:
0.0000471
AC:
7
AN:
148584
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000171
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000165
AC:
4
AN:
242876
Hom.:
0
AF XY:
0.0000152
AC XY:
2
AN XY:
131844
show subpopulations
Gnomad AFR exome
AF:
0.000188
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:
0.00000890
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000624
AC:
9
AN:
1442726
Hom.:
0
Cov.:
31
AF XY:
0.00000418
AC XY:
3
AN XY:
717876
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
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:
0.00000362
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000471
AC:
7
AN:
148584
Hom.:
1
Cov.:
31
AF XY:
0.0000277
AC XY:
2
AN XY:
72252
show subpopulations
Gnomad4 AFR
AF:
0.000171
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680
ExAC
AF:
0.0000168
AC:
2

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 submitterclinical testingAmbry GeneticsMar 29, 2023The c.83A>G (p.Y28C) alteration is located in exon 2 (coding exon 2) of the APOBEC3B gene. This alteration results from a A to G substitution at nucleotide position 83, causing the tyrosine (Y) at amino acid position 28 to be replaced by a cysteine (C). 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
0.14
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
0.018
DANN
Benign
0.26
DEOGEN2
Benign
0.028
.;T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0046
N
LIST_S2
Benign
0.58
T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.4
L;.;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.12
Sift
Benign
0.16
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.0010
.;.;B
Vest4
0.14
MutPred
0.42
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.37
MPC
1.6
ClinPred
0.18
T
GERP RS
-4.9
Varity_R
0.084
gMVP
0.62

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: rs755159659; hg19: chr22-39380145; API