Variant chr22-38991444-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004900.5(APOBEC3B):c.836T>G(p.Ile279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.836T>G	p.Ile279Ser	missense_variant	6/8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.761T>G	p.Ile254Ser	missense_variant	6/8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 link	c.836T>G	p.Ile279Ser	missense_variant	6/8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 link	c.761T>G	p.Ile254Ser	missense_variant	6/8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 link	n.682T>G		non_coding_transcript_exon_variant	5/7	1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 link	c.836T>G	p.Ile279Ser	missense_variant	6/7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147744

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

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:

0.000502

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441620

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000715

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000338

AC:

AN:

147744

Hom.:

Cov.:

AF XY:

0.0000557

AC XY:

AN XY:

71790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000281

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:

0.000502

Bravo

AF:

0.0000529

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 submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.836T>G (p.I279S) alteration is located in exon 6 (coding exon 6) of the APOBEC3B gene. This alteration results from a T to G substitution at nucleotide position 836, causing the isoleucine (I) at amino acid position 279 to be replaced by a serine (S). 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

0.63

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

.;T;T

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.37

T;D;D

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.22

Sift

Benign

0.040

D;D;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.67

.;.;P

Vest4

0.36

MutPred

0.74

.;Gain of catalytic residue at I279 (P = 0.0057);Gain of catalytic residue at I279 (P = 0.0057);

MVP

0.75

MPC

3.6

ClinPred

0.89

GERP RS

0.87

Varity_R

0.47

gMVP

0.51

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