22-38961448-T-C

Variant names:

• chr22-38961448-T-C
• NM_145699.4:c.236T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_145699.4(APOBEC3A):​c.236T>C​(p.Val79Ala) variant causes a missense change. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.236T>C	p.Val79Ala	missense	Exon 3 of 5	NP_663745.1	P31941-1
	APOBEC3A	NM_001270406.2		c.182T>C	p.Val61Ala	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.236T>C	p.Val79Ala	missense	Exon 3 of 5	ENSP00000249116.2	P31941-1
	APOBEC3A	ENST00000402255.5	TSL:5	c.236T>C	p.Val79Ala	missense	Exon 4 of 6	ENSP00000384359.1	P31941-1
	ENSG00000305420	ENST00000810842.1		n.852A>G		non_coding_transcript_exon	Exon 4 of 4

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

African (AFR) AF: 0.00 AC: 0 AN: 26928

American (AMR) AF: 0.00 AC: 0 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24592

East Asian (EAS) AF: 0.00 AC: 0 AN: 38110

South Asian (SAS) AF: 0.00 AC: 0 AN: 79880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3918

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 935296

Other (OTH) AF: 0.00 AC: 0 AN: 53198

GnomAD4 genome Cov.: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.65	P
Vest4		0.12
MutPred		0.81		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
Mutation Taster		=89/11	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

Other links and lift over

hg19: chr22-39357453;