Genetic Variant LCN12:p.Arg135Ser (chr9-136953919-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178536.4(LCN12):c.403C>A(p.Arg135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,332 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R135L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LCN12
NM_178536.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

0 publications found

Variant links:

Genes affected

LCN12 (HGNC:28733): (lipocalin 12) Members of the lipocalin family, such as LCN12, have a common structure consisting of an 8-stranded antiparallel beta-barrel that forms a cup-shaped ligand-binding pocket or calyx. Lipocalins generally bind small hydrophobic ligands and transport them to specific cells (Suzuki et al., 2004 [PubMed 15363845]).[supplied by OMIM, Aug 2009]

LCN12 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LCN12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19778147).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178536.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN12	NM_178536.4	MANE Select	c.403C>A	p.Arg135Ser	missense	Exon 4 of 6	NP_848631.2	Q6JVE5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LCN12	ENST00000371633.8	TSL:1 MANE Select	c.403C>A	p.Arg135Ser	missense	Exon 4 of 6	ENSP00000360696.3	Q6JVE5
LCN12	ENST00000874070.1		c.403C>A	p.Arg135Ser	missense	Exon 5 of 7	ENSP00000544129.1
LCN12	ENST00000874069.1		c.331+140C>A		intron	N/A	ENSP00000544128.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111778

Other (OTH)

AF:

0.00

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.9

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.43

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-3.6

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.3

REVEL

Benign

0.035

Sift

Benign

0.036

Sift4G

Benign

0.064

Polyphen

0.98

Vest4

0.20

MutPred

0.53

Loss of MoRF binding (P = 0.0235)

MVP

0.28

MPC

0.50

ClinPred

0.56

GERP RS

0.15

Varity_R

0.16

gMVP

0.59

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over