Genetic Variant NM_019101.3:c.266G>T (chr6-31656623-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019101.3(APOM):c.266G>T(p.Arg89Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APOM
NM_019101.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

APOM (HGNC:13916): (apolipoprotein M) The protein encoded by this gene is an apolipoprotein and member of the lipocalin protein family. It is found associated with high density lipoproteins and to a lesser extent with low density lipoproteins and triglyceride-rich lipoproteins. The encoded protein is secreted through the plasma membrane but remains membrane-bound, where it is involved in lipid transport. Alternate splicing results in both coding and non-coding variants of this gene. [provided by RefSeq, Jan 2012]

APOM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOM	NM_019101.3 link	c.266G>T	p.Arg89Leu	missense_variant	Exon 2 of 6	ENST00000375916.4	NP_061974.2	O95445-1
APOM	NM_001256169.2 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 6		NP_001243098.1	O95445-2A0A1U9X793
APOM	XM_006715150.4 link	c.163G>T	p.Ala55Ser	missense_variant	Exon 2 of 6		XP_006715213.1
APOM	NR_045828.2 link	n.300G>T		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOM	ENST00000375916.4 link	c.266G>T	p.Arg89Leu	missense_variant	Exon 2 of 6	1	NM_019101.3	ENSP00000365081.3	O95445-1
APOM	ENST00000375920.8 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 6	1		ENSP00000365085.4	O95445-2
APOM	ENST00000375918.6 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 5	2		ENSP00000365083.2	Q5SRP5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726858

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;D

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.097

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.88

MutPred

0.57

.;.;Loss of MoRF binding (P = 0.0072);

MVP

0.58

MPC

0.99

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.73

gMVP

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over