12-56361843-C-G

Variant names:

• chr12-56361843-C-G
• rs767971917
• NM_001638.4:c.363G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001638.4(APOF):​c.363G>C​(p.Gln121His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: APOF NM_001638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• Publications: 0 publications found

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]

ENSG00000307495 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34331512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001638.4. 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
	APOF	NM_001638.4	MANE Select	c.363G>C	p.Gln121His	missense	Exon 2 of 2	NP_001629.1	Q13790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	ENST00000398189.4	TSL:1 MANE Select	c.363G>C	p.Gln121His	missense	Exon 2 of 2	ENSP00000381250.3	Q13790
	APOF	ENST00000887741.1		c.402G>C	p.Gln134His	missense	Exon 2 of 2	ENSP00000557800.1
	APOF	ENST00000887742.1		c.348G>C	p.Gln116His	missense	Exon 2 of 2	ENSP00000557801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461290 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726886

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.84
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.49		Gain of catalytic residue at V117 (P = 8e-04)
MVP		0.68
MPC		0.48
ClinPred		0.94	D
GERP RS		1.9
Varity_R		0.24
gMVP		0.24
Mutation Taster		=81/19	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: rs767971917; hg19: chr12-56755627;