chr22-38959558-C-A

Variant names:

• chr22-38959558-C-A
• NM_145699.4:c.46C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145699.4(APOBEC3A):​c.46C>A​(p.His16Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOBEC3A NM_145699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045701385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3A	NM_145699.4	c.46C>A	p.His16Asn	missense_variant	Exon 2 of 5	ENST00000249116.7	NP_663745.1
APOBEC3A	NM_001270406.2	c.30-38C>A		intron_variant	Intron 1 of 4		NP_001257335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3A	ENST00000249116.7	c.46C>A	p.His16Asn	missense_variant	Exon 2 of 5	1	NM_145699.4	ENSP00000249116.2
APOBEC3A	ENST00000402255.5	c.46C>A	p.His16Asn	missense_variant	Exon 3 of 6	5		ENSP00000384359.1
APOBEC3A	ENST00000488758.1	n.216C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0010
DANN	Benign	0.30
DEOGEN2	Benign	0.0016	T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.029	.;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.53	N;N;N
PROVEAN	Benign	0.16	N;N;.
REVEL	Benign	0.011
Sift	Benign	0.41	T;T;.
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.058
MutPred		0.30		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.34
MPC		0.0097
ClinPred		0.037	T
GERP RS		-4.5
Varity_R		0.089
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39355563;