22-38961418-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145699.4(APOBEC3A):c.206G>A(p.Arg69His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000914 in 1,204,158 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000079 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000091 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3A
NM_145699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25814742).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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>A	p.Arg69His	missense	Exon 3 of 5	NP_663745.1	P31941-1
	APOBEC3A	NM_001270406.2		c.152G>A	p.Arg51His	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>A	p.Arg69His	missense	Exon 3 of 5	ENSP00000249116.2	P31941-1
APOBEC3A	ENST00000402255.5	TSL:5	c.206G>A	p.Arg69His	missense	Exon 4 of 6	ENSP00000384359.1	P31941-1
ENSG00000305420	ENST00000810842.1		n.882C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000792

AC:

AN:

126306

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000163

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000953

AC:

AN:

209934

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000626

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000914

AC:

AN:

1204158

Hom.:

Cov.:

AF XY:

0.00000660

AC XY:

AN XY:

605948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25276

American (AMR)

AF:

0.0000696

AC:

AN:

43074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24068

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37696

South Asian (SAS)

AF:

0.0000383

AC:

AN:

78324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3604

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

889678

Other (OTH)

AF:

0.00

AC:

AN:

51250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000792

AC:

AN:

126306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60648

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28880

American (AMR)

AF:

0.00

AC:

AN:

13056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3166

East Asian (EAS)

AF:

0.00

AC:

AN:

4400

South Asian (SAS)

AF:

0.00

AC:

AN:

3554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000163

AC:

AN:

61302

Other (OTH)

AF:

0.00

AC:

AN:

1748

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000874

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.036

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

M_CAP

Benign

0.020

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

PhyloP100

2.1

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.16

Polyphen

0.046

Vest4

0.061

MutPred

0.70

Loss of methylation at R69 (P = 0.0584)

MVP

0.71

MPC

2.2

ClinPred

0.037

GERP RS

1.3

Varity_R

0.17

gMVP

0.21

Mutation Taster

=92/8

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over