chr22-38991446-T-A

Position:

• chr22-38991446-T-A

Variant summary

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

The ENST00000333467.4(APOBEC3B):​c.838T>A​(p.Ser280Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: APOBEC3B ENST00000333467.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62

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]

ACMG classification

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	c.838T>A	p.Ser280Thr	missense_variant	6/8	ENST00000333467.4	NP_004891.5
APOBEC3B	NM_001270411.2	c.763T>A	p.Ser255Thr	missense_variant	6/8		NP_001257340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4	c.838T>A	p.Ser280Thr	missense_variant	6/8	1	NM_004900.5	ENSP00000327459	P2
APOBEC3B	ENST00000407298.7	c.763T>A	p.Ser255Thr	missense_variant	6/8	1		ENSP00000385068
APOBEC3B	ENST00000335760.9	c.684T>A	p.Ser228=	synonymous_variant, NMD_transcript_variant	5/7	1		ENSP00000338897
APOBEC3B	ENST00000402182.7	c.838T>A	p.Ser280Thr	missense_variant	6/7	2		ENSP00000385060	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.838T>A (p.S280T) alteration is located in exon 6 (coding exon 6) of the APOBEC3B gene. This alteration results from a T to A substitution at nucleotide position 838, causing the serine (S) at amino acid position 280 to be replaced by a threonine (T). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	.;T;T
Eigen	Benign	0.056
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	.;.;M
MutationTaster	Benign	0.68	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;T;D
Sift4G	Benign	0.24	T;T;T
Polyphen		0.99	.;.;D
Vest4		0.42
MutPred		0.88		.;Gain of glycosylation at S280 (P = 0.1264);Gain of glycosylation at S280 (P = 0.1264);
MVP		0.64
MPC		2.5
ClinPred		0.70	D
GERP RS		0.80
Varity_R		0.49
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39387451;