rs191285090

Variant names:

• chr12-7651112-T-A
• NM_001644.5:c.472A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-7651112-T-A
• chr12-7651112-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001644.5(APOBEC1):​c.472A>T​(p.Asn158Tyr) 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 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOBEC1 NM_001644.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38044286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC1	NM_001644.5	c.472A>T	p.Asn158Tyr	missense_variant	Exon 4 of 5	ENST00000229304.5	NP_001635.2
APOBEC1	NM_001304566.1	c.472A>T	p.Asn158Tyr	missense_variant	Exon 5 of 6		NP_001291495.1
APOBEC1	NM_005889.4	c.337A>T	p.Asn113Tyr	missense_variant	Exon 3 of 4		NP_005880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC1	ENST00000229304.5	c.472A>T	p.Asn158Tyr	missense_variant	Exon 4 of 5	1	NM_001644.5	ENSP00000229304.4
APOBEC1	ENST00000467171.2	n.*333A>T		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000436415.2
APOBEC1	ENST00000467171.2	n.*333A>T		3_prime_UTR_variant	Exon 3 of 4	1		ENSP00000436415.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.89	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.60	N
REVEL	Uncertain	0.33
Sift	Benign	0.41	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.59		Gain of phosphorylation at N158 (P = 0.0641);
MVP		0.80
MPC		1.1
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.17
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-7803708;