22-38989481-C-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_004900.5(APOBEC3B):c.594C>G(p.Phe198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,581,098 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000028 ( 4 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.142

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.594C>G	p.Phe198Leu	missense_variant	Exon 5 of 8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.594C>G	p.Phe198Leu	missense_variant	Exon 5 of 8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 link	c.594C>G	p.Phe198Leu	missense_variant	Exon 5 of 8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 link	c.594C>G	p.Phe198Leu	missense_variant	Exon 5 of 8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 link	n.570-1851C>G		intron_variant	Intron 4 of 6	1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 link	c.594C>G	p.Phe198Leu	missense_variant	Exon 5 of 7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.0000337

AC:

AN:

148504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

244406

Hom.:

AF XY:

0.0000226

AC XY:

AN XY:

132476

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1432594

Hom.:

Cov.:

AF XY:

0.0000239

AC XY:

AN XY:

710636

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

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:

0.0000380

Gnomad4 NFE exome

AF:

0.0000301

Gnomad4 OTH exome

AF:

0.0000511

GnomAD4 genome

AF:

0.0000337

AC:

AN:

148504

Hom.:

Cov.:

AF XY:

0.0000416

AC XY:

AN XY:

72184

show subpopulations

Gnomad4 AFR

AF:

0.0000490

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:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000503

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.594C>G (p.F198L) alteration is located in exon 5 (coding exon 5) of the APOBEC3B gene. This alteration results from a C to G substitution at nucleotide position 594, causing the phenylalanine (F) at amino acid position 198 to be replaced by a leucine (L). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

.;T;D

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.90

D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

4.0

H;.;H

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.39

MutPred

0.90

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.87

MPC

0.81

ClinPred

0.88

GERP RS

0.88

Varity_R

0.68

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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