chr12-56361583-C-A

Variant names:

• chr12-56361583-C-A
• NM_001638.4:c.623G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001638.4(APOF):​c.623G>T​(p.Gly208Val) 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. 16/22 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: APOF NM_001638.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.410
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09643617).

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.623G>T	p.Gly208Val	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.623G>T	p.Gly208Val	missense	Exon 2 of 2	ENSP00000381250.3	Q13790
	APOF	ENST00000887741.1		c.662G>T	p.Gly221Val	missense	Exon 2 of 2	ENSP00000557800.1
	APOF	ENST00000887742.1		c.608G>T	p.Gly203Val	missense	Exon 2 of 2	ENSP00000557801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.41
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.041
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.017	D
Polyphen		0.41	B
Vest4		0.13
MutPred		0.40		Gain of catalytic residue at Q204 (P = 0.0022)
MVP		0.36
MPC		0.13
ClinPred		0.23	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.26
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr12-56755367;