rs5742904

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2_SupportingPM5PP3_StrongPP5

The NM_000384(APOB):c.10580G>T(p.Arg3527Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3527W) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

APOB
NM_000384 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.11

Links

APOB (HGNC:603):

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 33.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-21006288-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 17890. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.972

PP5

Variant 2:21006288-C>A is Pathogenic according to our data. Variant chr2-21006288-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 440523. Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-21006288-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOB	NM_000384.3 linkuse as main transcript	c.10580G>T	p.Arg3527Leu	missense_variant	26/29	ENST00000233242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOB	ENST00000233242.5 linkuse as main transcript	c.10580G>T	p.Arg3527Leu	missense_variant	26/29	1	NM_000384.3	P1

Frequencies

GnomAD3 genomes

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.46

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Vest4

0.83

MutPred

0.86

Loss of MoRF binding (P = 0.0054);

MVP

0.94

MPC

0.29

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.84

Splicing

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over