12-7649609-T-C

Variant names:

• chr12-7649609-T-C
• NM_001644.5:c.649A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001644.5(APOBEC1):​c.649A>G​(p.Thr217Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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)
• Consequence: APOBEC1 NM_001644.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.402
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046984643).

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.649A>G	p.Thr217Ala	missense	Exon 5 of 5	NP_001635.2	P41238
	APOBEC1	NM_001304566.1		c.649A>G	p.Thr217Ala	missense	Exon 6 of 6	NP_001291495.1	P41238
	APOBEC1	NM_005889.4		c.514A>G	p.Thr172Ala	missense	Exon 4 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.649A>G	p.Thr217Ala	missense	Exon 5 of 5	ENSP00000229304.4	P41238
	APOBEC1	ENST00000467171.2	TSL:1	n.*510A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000436415.2	A0A0B4J232
	APOBEC1	ENST00000467171.2	TSL:1	n.*510A>G		3_prime_UTR	Exon 4 of 4	ENSP00000436415.2	A0A0B4J232

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.067
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.0
DANN	Benign	0.71
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.40
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.071
Sift	Benign	0.66	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.31		Loss of glycosylation at T217 (P = 0.0489)
MVP		0.59
MPC		0.31
ClinPred		0.017	T
GERP RS		1.9
Varity_R		0.21
gMVP		0.22
Mutation Taster		=98/2	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

hg19: chr12-7802205;