NM_004900.5:c.325T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004900.5(APOBEC3B):c.325T>G(p.Ser109Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,599,074 control chromosomes in the GnomAD database, including 447 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0046 ( 35 hom., cov: 28)

Exomes 𝑓: 0.0053 ( 412 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006128192).

BP6

Variant 22-38985962-T-G is Benign according to our data. Variant chr22-38985962-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 link	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 link	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 link	n.325T>G		non_coding_transcript_exon_variant	Exon 3 of 7	1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 link	c.325T>G	p.Ser109Ala	missense_variant	Exon 3 of 7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

684

AN:

147604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.000692

Gnomad SAS

AF:

0.00317

Gnomad FIN

AF:

0.000777

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00659

Gnomad OTH

AF:

0.00555

GnomAD3 exomes

AF:

0.00302

AC:

752

AN:

248958

Hom.:

AF XY:

0.00329

AC XY:

443

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000287

Gnomad SAS exome

AF:

0.00267

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00526

AC:

7638

AN:

1451398

Hom.:

412

Cov.:

AF XY:

0.00525

AC XY:

3792

AN XY:

721974

show subpopulations

Gnomad4 AFR exome

AF:

0.00357

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.000380

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.00190

Gnomad4 NFE exome

AF:

0.00608

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.00465

AC:

686

AN:

147676

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

312

AN XY:

71832

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000579

Gnomad4 EAS

AF:

0.000695

Gnomad4 SAS

AF:

0.00317

Gnomad4 FIN

AF:

0.000777

Gnomad4 NFE

AF:

0.00659

Gnomad4 OTH

AF:

0.00556

Alfa

AF:

0.00513

Hom.:

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00366

AC:

444

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APOBEC3A: BS2; APOBEC3B: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.023

DANN

Benign

0.16

DEOGEN2

Benign

0.0011

.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.18

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.069

MVP

0.29

MPC

1.1

ClinPred

0.00028

GERP RS

-2.9

Varity_R

0.087

gMVP

0.091

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