Genetic Variant APOBEC3A:p.Arg144Trp (chr22-38961642-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145699.4(APOBEC3A):c.430C>T(p.Arg144Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000058 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000012 ( 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: 0.341

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15446988).

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.430C>T	p.Arg144Trp	missense	Exon 3 of 5	NP_663745.1	P31941-1
	APOBEC3A	NM_001270406.2		c.376C>T	p.Arg126Trp	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.430C>T	p.Arg144Trp	missense	Exon 3 of 5	ENSP00000249116.2	P31941-1
APOBEC3A	ENST00000402255.5	TSL:5	c.430C>T	p.Arg144Trp	missense	Exon 4 of 6	ENSP00000384359.1	P31941-1
ENSG00000305420	ENST00000810842.1		n.658G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000583

AC:

AN:

137214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000218

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000470

AC:

AN:

212910

AF XY:

0.0000524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000649

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000207

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000118

AC:

AN:

1269334

Hom.:

Cov.:

AF XY:

0.00000793

AC XY:

AN XY:

630474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24986

American (AMR)

AF:

0.000248

AC:

AN:

40328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21584

East Asian (EAS)

AF:

0.0000622

AC:

AN:

32146

South Asian (SAS)

AF:

0.00

AC:

AN:

76964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4570

European-Non Finnish (NFE)

AF:

0.00000206

AC:

AN:

973036

Other (OTH)

AF:

0.0000197

AC:

AN:

50804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.0000583

AC:

AN:

137214

Hom.:

Cov.:

AF XY:

0.0000759

AC XY:

AN XY:

65900

show subpopulations

African (AFR)

AF:

0.0000283

AC:

AN:

35306

American (AMR)

AF:

0.000459

AC:

AN:

13080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3352

East Asian (EAS)

AF:

0.000218

AC:

AN:

4594

South Asian (SAS)

AF:

0.00

AC:

AN:

4050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65038

Other (OTH)

AF:

0.00

AC:

AN:

1894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000271

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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.042

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.22

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.93

PhyloP100

0.34

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.045

Sift

Uncertain

0.0040

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.059

MutPred

0.42

Gain of catalytic residue at Q141 (P = 0.1564)

MVP

0.42

MPC

1.7

ClinPred

0.15

GERP RS

-2.0

Varity_R

0.27

gMVP

0.36

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over