Genetic Variant APOM:c.541+7G>A (chr6-31657730-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019101.3(APOM):c.541+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

APOM
NM_019101.3 splice_region, intron

Scores

Splicing: ADA: 0.00001500

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.862

Publications

26 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.29703164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019101.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOM	NM_019101.3	MANE Select	c.541+7G>A	splice_region intron	N/A	NP_061974.2
APOM	NM_001256169.2		c.325+7G>A	splice_region intron	N/A	NP_001243098.1
APOM	NR_045828.2		n.582+7G>A	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
APOM	ENST00000375916.4	TSL:1 MANE Select	c.541+7G>A		splice_region intron	N/A	ENSP00000365081.3
APOM	ENST00000375920.8	TSL:1	c.325+7G>A		splice_region intron	N/A	ENSP00000365085.4
APOM	ENST00000375918.6	TSL:2	c.332G>A	p.Gly111Glu	missense	Exon 5 of 5	ENSP00000365083.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33288

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106382

Other (OTH)

AF:

0.00

AC:

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.6

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.022

Eigen

Benign

0.18

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.28

M_CAP

Benign

0.0063

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.96

PhyloP100

0.86

PROVEAN

Benign

1.8

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Vest4

0.12

MutPred

0.19

Loss of loop (P = 0.0112)

MVP

0.73

ClinPred

0.21

GERP RS

2.7

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0040

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over