Variant 3-100451871-A-T 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.309A>T(p.Arg103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000859 in 1,304,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

LNP1
ENST00000383693.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.840

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=0.014813125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNP1	NM_001085451.2 linkuse as main transcript	c.309A>T	p.Arg103Ser	missense_variant	3/4	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.309A>T	p.Arg103Ser	missense_variant	3/4	1	NM_001085451.2	ENSP00000373191	P1
LNP1	ENST00000489752.1 linkuse as main transcript	c.348A>T	p.Arg116Ser	missense_variant	3/4	5		ENSP00000417985
LNP1	ENST00000466996.5 linkuse as main transcript	c.*121A>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	5		ENSP00000419213

Frequencies

GnomAD3 genomes

AF:

0.000661

AC:

AN:

83262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000644

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:

0.00

Gnomad OTH

AF:

0.000885

GnomAD3 exomes

AF:

0.0000682

AC:

AN:

249118

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.000841

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000467

AC:

AN:

1220784

Hom.:

Cov.:

AF XY:

0.0000533

AC XY:

AN XY:

600892

show subpopulations

Gnomad4 AFR exome

AF:

0.00166

Gnomad4 AMR exome

AF:

0.000149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000169

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.000660

AC:

AN:

83338

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

AN XY:

40460

show subpopulations

Gnomad4 AFR

AF:

0.00199

Gnomad4 AMR

AF:

0.000644

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000882

Alfa

AF:

0.0000377

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.000813

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000828

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 17, 2023

The c.309A>T (p.R103S) alteration is located in exon 3 (coding exon 2) of the LNP1 gene. This alteration results from a A to T substitution at nucleotide position 309, causing the arginine (R) at amino acid position 103 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

0.85

N;N

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.024

Sift

Uncertain

0.013

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.48

P;.

Vest4

0.17

MutPred

0.18

Gain of glycosylation at S104 (P = 2e-04);.;

MVP

0.072

MPC

0.22

ClinPred

0.054

GERP RS

2.9

Varity_R

0.26

gMVP

0.063

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