Genetic Variant APOBEC3A:p.Arg69Leu (chr22-38961418-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145699.4(APOBEC3A):c.206G>T(p.Arg69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 18)

Consequence

APOBEC3A
NM_145699.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Publications

2 publications found

Variant links:

Genes affected

APOBEC3A (HGNC:17343): (apolipoprotein B mRNA editing enzyme catalytic subunit 3A) 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. The protein encoded by this gene lacks the zinc binding activity of other family members. The protein plays a role in immunity, by restricting transmission of foreign DNA such as viruses. One mechanism of foreign DNA restriction is deamination of foreign double-stranded DNA cytidines to uridines, which leads to DNA degradation. However, other mechanisms are also thought to be involved, as anti-viral effect is not dependent on deaminase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

APOBEC3A links:

ENSG00000305420 (HGNC:):

ENSG00000305420 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37575674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145699.4. 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
	APOBEC3A	NM_145699.4	MANE Select	c.206G>T	p.Arg69Leu	missense	Exon 3 of 5	NP_663745.1	P31941-1
	APOBEC3A	NM_001270406.2		c.152G>T	p.Arg51Leu	missense	Exon 3 of 5	NP_001257335.1	B7ZLZ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3A	ENST00000249116.7	TSL:1 MANE Select	c.206G>T	p.Arg69Leu	missense	Exon 3 of 5	ENSP00000249116.2	P31941-1
APOBEC3A	ENST00000402255.5	TSL:5	c.206G>T	p.Arg69Leu	missense	Exon 4 of 6	ENSP00000384359.1	P31941-1
ENSG00000305420	ENST00000810842.1		n.882C>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.036

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.55

M_CAP

Benign

0.024

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.8

PhyloP100

2.1

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.40

Vest4

0.10

MutPred

0.70

Loss of methylation at R69 (P = 0.0584)

MVP

0.74

MPC

2.4

ClinPred

0.092

GERP RS

1.3

Varity_R

0.24

gMVP

0.28

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over