22-38961448-T-C

Position:

• chr22-38961448-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_145699.4(APOBEC3A):​c.236T>C​(p.Val79Ala) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOBEC3A NM_145699.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3A	NM_145699.4	c.236T>C	p.Val79Ala	missense_variant	3/5	ENST00000249116.7	NP_663745.1
APOBEC3A	NM_001270406.2	c.182T>C	p.Val61Ala	missense_variant	3/5		NP_001257335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3A	ENST00000249116.7	c.236T>C	p.Val79Ala	missense_variant	3/5	1	NM_145699.4	ENSP00000249116.2
APOBEC3A	ENST00000402255.5	c.236T>C	p.Val79Ala	missense_variant	4/6	5		ENSP00000384359.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.95e-7 AC: 1 AN: 1257252 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 631754

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.236T>C (p.V79A) alteration is located in exon 3 (coding exon 3) of the APOBEC3A gene. This alteration results from a T to C substitution at nucleotide position 236, causing the valine (V) at amino acid position 79 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.042	T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.67	.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;M;M
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.65	P;P;P
Vest4		0.12
MutPred		0.81		Loss of stability (P = 0.0443);Loss of stability (P = 0.0443);Loss of stability (P = 0.0443);
MVP		0.58
MPC		2.3
ClinPred		0.35	T
GERP RS		2.4
Varity_R		0.34
gMVP		0.24

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: chr22-39357453;