12-56361452-C-T

Position:

• chr12-56361452-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001638.4(APOF):​c.754G>A​(p.Gly252Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOF NM_001638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59

Genes affected

APOF (HGNC:615): (apolipoprotein F) The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOF	NM_001638.4	c.754G>A	p.Gly252Arg	missense_variant	2/2	ENST00000398189.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOF	ENST00000398189.4	c.754G>A	p.Gly252Arg	missense_variant	2/2	1	NM_001638.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.72
MutPred		0.44		Gain of MoRF binding (P = 0.0342);
MVP		0.65
MPC		0.57
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.71
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr12-56755236;