9-136954230-C-A

Variant names:

• chr9-136954230-C-A
• rs1180317296
• NM_178536.4:c.525C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178536.4(LCN12):​c.525C>A​(p.Asp175Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCN12 NM_178536.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.84
• Publications: 0 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: 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=0.14663157).

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.525C>A	p.Asp175Glu	missense	Exon 5 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.525C>A	p.Asp175Glu	missense	Exon 5 of 6	ENSP00000360696.3	Q6JVE5
	LCN12	ENST00000874070.1		c.525C>A	p.Asp175Glu	missense	Exon 6 of 7	ENSP00000544129.1
	LCN12	ENST00000874069.1		c.408C>A	p.Asp136Glu	missense	Exon 5 of 6	ENSP00000544128.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000528 AC: 1 AN: 189498 AF XY: 0.00000983

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425232 Hom.: 0 Cov.: 51 AF XY: 0.00000284 AC XY: 2 AN XY: 705464

African (AFR) AF: 0.00 AC: 0 AN: 32562

American (AMR) AF: 0.00 AC: 0 AN: 40194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25446

East Asian (EAS) AF: 0.00 AC: 0 AN: 37646

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092948

Other (OTH) AF: 0.00 AC: 0 AN: 58968

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.39
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
PhyloP100		-2.8
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.068
Sift	Benign	0.080	T
Sift4G	Benign	0.26	T
Polyphen		0.77	P
Vest4		0.035
MutPred		0.60		Loss of stability (P = 0.2368)
MVP		0.35
MPC		0.15
ClinPred		0.19	T
GERP RS		-0.63
Varity_R		0.050
gMVP		0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1180317296; hg19: chr9-139848682;