Genetic Variant LCN2:p.Met140Thr (chr9-128151969-T-C) – 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_005564.5(LCN2):c.419T>C(p.Met140Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

LCN2
NM_005564.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.388

Variant links:

Genes affected

LCN2 (HGNC:6526): (lipocalin 2) This gene encodes a protein that belongs to the lipocalin family. Members of this family transport small hydrophobic molecules such as lipids, steroid hormones and retinoids. The protein encoded by this gene is a neutrophil gelatinase-associated lipocalin and plays a role in innate immunity by limiting bacterial growth as a result of sequestering iron-containing siderophores. The presence of this protein in blood and urine is an early biomarker of acute kidney injury. This protein is thought to be be involved in multiple cellular processes, including maintenance of skin homeostasis, and suppression of invasiveness and metastasis. Mice lacking this gene are more susceptible to bacterial infection than wild type mice. [provided by RefSeq, Sep 2015]

LCN2 links:

ENSG00000308297 (HGNC:):

ENSG00000308297 links:

Genome browser will be placed here

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=0.28301054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN2	NM_005564.5 link	c.419T>C	p.Met140Thr	missense_variant	Exon 4 of 7	ENST00000277480.7	NP_005555.2	P80188-1
LCN2	XM_047423376.1 link	c.419T>C	p.Met140Thr	missense_variant	Exon 4 of 6		XP_047279332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN2	ENST00000277480.7 link	c.419T>C	p.Met140Thr	missense_variant	Exon 4 of 7	1	NM_005564.5	ENSP00000277480.2		P80188-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111976

Other (OTH)

AF:

0.0000497

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.419T>C (p.M140T) alteration is located in exon 4 (coding exon 4) of the LCN2 gene. This alteration results from a T to C substitution at nucleotide position 419, causing the methionine (M) at amino acid position 140 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.2

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.27

T;T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.51

.;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;L;.

PhyloP100

0.39

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.040

Sift

Benign

0.13

T;T;T

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.14

B;B;.

Vest4

0.41

MutPred

0.71

Loss of stability (P = 0.0564);Loss of stability (P = 0.0564);.;

MVP

0.061

MPC

0.037

ClinPred

0.050

GERP RS

0.23

Varity_R

0.46

gMVP

0.57

Mutation Taster

=56/44

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-128151969-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over