Genetic Variant APOBEC3B:p.Arg327Gly (chr22-38991587-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004900.5(APOBEC3B):c.979C>G(p.Arg327Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R327W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000015 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

Publications

0 publications found

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]

APOBEC3B links:

APOBEC3B-AS1 (HGNC:43836): (APOBEC3B antisense RNA 1)

APOBEC3B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16750902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004900.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3B	NM_004900.5	MANE Select	c.979C>G	p.Arg327Gly	missense	Exon 6 of 8	NP_004891.5
APOBEC3B	NM_001270411.2		c.904C>G	p.Arg302Gly	missense	Exon 6 of 8	NP_001257340.2	Q9UH17-3
APOBEC3B-AS1	NR_104187.1		n.674G>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.979C>G	p.Arg327Gly	missense	Exon 6 of 8	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7	TSL:1	c.904C>G	p.Arg302Gly	missense	Exon 6 of 8	ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9	TSL:1	n.*69C>G		non_coding_transcript_exon	Exon 5 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000147

AC:

AN:

1356888

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

674268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29920

American (AMR)

AF:

0.00

AC:

AN:

39022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22724

East Asian (EAS)

AF:

0.0000663

AC:

AN:

30164

South Asian (SAS)

AF:

0.00

AC:

AN:

83568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047030

Other (OTH)

AF:

0.00

AC:

AN:

53538

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.2

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.019

Eigen

Benign

-0.78

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.098

M_CAP

Benign

0.0087

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PhyloP100

0.033

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Benign

0.27

Sift4G

Benign

0.40

Polyphen

0.55

Vest4

0.17

MutPred

0.59

Gain of catalytic residue at M325 (P = 0.0357)

MVP

0.51

MPC

3.4

ClinPred

0.29

GERP RS

-3.8

Varity_R

0.17

gMVP

0.23

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over