NM_001644.5:c.52A>G

Variant names:

• chr12-7652828-T-C
• rs1565440016
• NM_001644.5:c.52A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001644.5(APOBEC1):​c.52A>G​(p.Ile18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: APOBEC1 NM_001644.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

Genes affected

APOBEC1 (HGNC:604): (apolipoprotein B mRNA editing enzyme catalytic subunit 1) This gene encodes a member of the cytidine deaminase enzyme family. The encoded protein forms a multiple-protein editing holoenzyme with APOBEC1 complementation factor (ACF) and APOBEC1 stimulating protein (ASP). This holoenzyme is involved in the editing of C-to-U nucleotide bases in apolipoprotein B and neurofibromatosis-1 mRNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001644.5. 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
	APOBEC1	NM_001644.5	MANE Select	c.52A>G	p.Ile18Val	missense	Exon 3 of 5	NP_001635.2	P41238
	APOBEC1	NM_001304566.1		c.52A>G	p.Ile18Val	missense	Exon 4 of 6	NP_001291495.1	P41238
	APOBEC1	NM_005889.4		c.-84A>G		5_prime_UTR	Exon 2 of 4	NP_005880.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC1	ENST00000229304.5	TSL:1 MANE Select	c.52A>G	p.Ile18Val	missense	Exon 3 of 5	ENSP00000229304.4	P41238
	APOBEC1	ENST00000467171.2	TSL:1	n.24A>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000436415.2	A0A0B4J232

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425990 Hom.: 0 Cov.: 36 AF XY: 0.00000142 AC XY: 1 AN XY: 705944

African (AFR) AF: 0.00 AC: 0 AN: 31734

American (AMR) AF: 0.00 AC: 0 AN: 38540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 81690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095526

Other (OTH) AF: 0.00 AC: 0 AN: 58762

GnomAD4 genome Cov.: 32

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	0.22
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.26
Sift	Benign	0.080	T
Sift4G	Uncertain	0.047	D
Polyphen		0.97	D
Vest4		0.30
MutPred		0.72		Loss of catalytic residue at P20 (P = 0.0306)
MVP		0.71
MPC		0.95
ClinPred		0.92	D
GERP RS		3.3
Varity_R		0.11
gMVP		0.26
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1565440016; hg19: chr12-7805424;