Variant 3-100455847-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000383693.8(LNP1):c.458T>C(p.Val153Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

LNP1
ENST00000383693.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.114

Variant links:

Genes affected

LNP1 (HGNC:28014): (leukemia NUP98 fusion partner 1)

LNP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026256502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNP1	NM_001085451.2 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	4/4	ENST00000383693.8	NP_001078920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LNP1	ENST00000383693.8 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	4/4	1	NM_001085451.2	ENSP00000373191	P1
LNP1	ENST00000489752.1 linkuse as main transcript	c.497T>C	p.Val166Ala	missense_variant	4/4	5		ENSP00000417985
LNP1	ENST00000466996.5 linkuse as main transcript	c.*270T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	5		ENSP00000419213

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000168

AC:

AN:

249514

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000217

AC:

317

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000749

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.000191

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000207

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.458T>C (p.V153A) alteration is located in exon 4 (coding exon 3) of the LNP1 gene. This alteration results from a T to C substitution at nucleotide position 458, causing the valine (V) at amino acid position 153 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.6

DANN

Benign

0.35

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.013

Sift

Benign

0.12

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0020

B;.

Vest4

0.045

MVP

0.014

MPC

0.21

ClinPred

0.0079

GERP RS

-1.3

Varity_R

0.038

gMVP

0.014

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over