APOBEC3A p.Gly108Arg

Variant names:

• chr22-38961534-G-C
• NM_145699.4:c.322G>C
• APOBEC3A p.Gly108Arg

Your query was ambiguous. Multiple possible variants found:

• chr22-38961534-G-C
• chr22-38961534-G-A
• chr22-38961534-GGG-CGT
• chr22-38961534-GGG-CGC
• chr22-38961534-GGG-CGA
• chr22-38961534-GGG-AGA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145699.4(APOBEC3A):​c.322G>C​(p.Gly108Arg) 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. 16/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 18)
• Consequence: APOBEC3A NM_145699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 0 publications found

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]

ENSG00000305420 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042906612).

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.322G>C	p.Gly108Arg	missense	Exon 3 of 5	NP_663745.1	P31941-1
	APOBEC3A	NM_001270406.2		c.268G>C	p.Gly90Arg	missense	Exon 3 of 5	NP_001257335.1	B7ZLZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3A	ENST00000249116.7	TSL:1 MANE Select	c.322G>C	p.Gly108Arg	missense	Exon 3 of 5	ENSP00000249116.2	P31941-1
	APOBEC3A	ENST00000402255.5	TSL:5	c.322G>C	p.Gly108Arg	missense	Exon 4 of 6	ENSP00000384359.1	P31941-1
	ENSG00000305420	ENST00000810842.1		n.766C>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.12
DANN	Benign	0.26
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-0.95
PROVEAN	Benign	1.6	N
REVEL	Benign	0.051
Sift	Benign	0.56	T
Sift4G	Benign	0.63	T
Varity_R		0.15
gMVP		0.19
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-39357539;