22-38991444-T-G

Variant names:

• chr22-38991444-T-G
• rs1261636123
• NM_004900.5:c.836T>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	NM_004900.5	MANE Select	c.836T>G	p.Ile279Ser	missense	Exon 6 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.761T>G	p.Ile254Ser	missense	Exon 6 of 8	NP_001257340.2	Q9UH17-3
	APOBEC3B-AS1	NR_104187.1		n.*115A>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.836T>G	p.Ile279Ser	missense	Exon 6 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.761T>G	p.Ile254Ser	missense	Exon 6 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.682T>G		non_coding_transcript_exon	Exon 5 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes AF: 0.0000338 AC: 5 AN: 147744 Hom.: 0 Cov.: 30

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: 3 AN: 1441620 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717418

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.0000715 AC: 3 AN: 41954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 35956

South Asian (SAS) AF: 0.00 AC: 0 AN: 84202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102330

Other (OTH) AF: 0.00 AC: 0 AN: 59334

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000338 AC: 5 AN: 147744 Hom.: 0 Cov.: 30 AF XY: 0.0000557 AC XY: 4 AN XY: 71790

African (AFR) AF: 0.00 AC: 0 AN: 40872

American (AMR) AF: 0.000281 AC: 4 AN: 14236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4410

South Asian (SAS) AF: 0.00 AC: 0 AN: 4440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66960

Other (OTH) AF: 0.000502 AC: 1 AN: 1992

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.8
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.22
Sift	Benign	0.040	D
Sift4G	Uncertain	0.041	D
Polyphen		0.67	P
Vest4		0.36
MutPred		0.74		Gain of catalytic residue at I279 (P = 0.0057)
MVP		0.75
MPC		3.6
ClinPred		0.89	D
GERP RS		0.87
Varity_R		0.47
gMVP		0.51
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1261636123; hg19: chr22-39387449;