12-7652817-C-T

Variant names:

• chr12-7652817-C-T
• rs199783827
• NM_001644.5:c.63G>A
• APOBEC1 p.Trp21*

Variant summary

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

The NM_001644.5(APOBEC1):​c.63G>A​(p.Trp21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: APOBEC1 NM_001644.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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.63G>A	p.Trp21*	stop_gained	Exon 3 of 5	NP_001635.2	P41238
	APOBEC1	NM_001304566.1		c.63G>A	p.Trp21*	stop_gained	Exon 4 of 6	NP_001291495.1	P41238
	APOBEC1	NM_005889.4		c.-73G>A		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.63G>A	p.Trp21*	stop_gained	Exon 3 of 5	ENSP00000229304.4	P41238
	APOBEC1	ENST00000467171.2	TSL:1	n.35G>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000436415.2	A0A0B4J232

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439338 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 713436

African (AFR) AF: 0.0000309 AC: 1 AN: 32350

American (AMR) AF: 0.00 AC: 0 AN: 41370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25462

East Asian (EAS) AF: 0.00 AC: 0 AN: 39354

South Asian (SAS) AF: 0.00 AC: 0 AN: 83522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100846

Other (OTH) AF: 0.00 AC: 0 AN: 59360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	35
DANN	Uncertain	0.98
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.093	N
PhyloP100		-0.062
Mutation Taster		=139/61	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs199783827;

hg19: chr12-7805413;