chr9-136953019-C-T

Variant names:

• chr9-136953019-C-T
• rs200323689
• NM_178536.4:c.242C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178536.4(LCN12):​c.242C>T​(p.Ala81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: LCN12 NM_178536.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062903106).

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.242C>T	p.Ala81Val	missense	Exon 2 of 6	NP_848631.2	Q6JVE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN12	ENST00000371633.8	TSL:1 MANE Select	c.242C>T	p.Ala81Val	missense	Exon 2 of 6	ENSP00000360696.3	Q6JVE5
	LCN12	ENST00000874070.1		c.242C>T	p.Ala81Val	missense	Exon 3 of 7	ENSP00000544129.1
	LCN12	ENST00000874069.1		c.242C>T	p.Ala81Val	missense	Exon 3 of 6	ENSP00000544128.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

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: 0.000470

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000273 AC: 68 AN: 248638 AF XY: 0.000281

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000936

Gnomad NFE exome AF: 0.000337

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000537 AC: 785 AN: 1461498 Hom.: 0 Cov.: 40 AF XY: 0.000528 AC XY: 384 AN XY: 727098

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000716 AC: 32 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000657 AC: 731 AN: 1111908

Other (OTH) AF: 0.000215 AC: 13 AN: 60374

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22 AN XY: 74378

African (AFR) AF: 0.0000724 AC: 3 AN: 41464

American (AMR) AF: 0.000589 AC: 9 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000366

ESP6500AA AF: 0.000231 AC: 1

ESP6500EA AF: 0.000823 AC: 7

ExAC AF: 0.000248 AC: 30

EpiCase AF: 0.000164

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.42	N
PhyloP100		2.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.91	T
Sift4G	Uncertain	0.029	D
Polyphen		0.90	P
Vest4		0.44
MVP		0.71
MPC		0.45
ClinPred		0.056	T
GERP RS		1.3
PromoterAI		-0.00070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.63
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200323689; hg19: chr9-139847471;