chr9-136953871-A-G

Variant names:

• chr9-136953871-A-G
• rs1851240471
• NM_178536.4:c.355A>G

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.355A>G​(p.Thr119Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,604,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LCN12 NM_178536.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18
• 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=0.094601214).

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.355A>G	p.Thr119Ala	missense	Exon 4 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.355A>G	p.Thr119Ala	missense	Exon 4 of 6	ENSP00000360696.3	Q6JVE5
	LCN12	ENST00000874070.1		c.355A>G	p.Thr119Ala	missense	Exon 5 of 7	ENSP00000544129.1
	LCN12	ENST00000874069.1		c.331+92A>G		intron	N/A	ENSP00000544128.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152072 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000478

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452264 Hom.: 0 Cov.: 53 AF XY: 0.00000139 AC XY: 1 AN XY: 721666

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 43282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25754

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.00 AC: 0 AN: 84764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108120

Other (OTH) AF: 0.0000167 AC: 1 AN: 60024

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152072 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000378

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	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.4
DANN	Benign	0.70
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.0030
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.058	T
Polyphen		0.24	B
Vest4		0.19
MutPred		0.47		Loss of phosphorylation at T119 (P = 0.0188)
MVP		0.088
MPC		0.14
ClinPred		0.13	T
GERP RS		-1.5
Varity_R		0.066
gMVP		0.42
Mutation Taster		=98/2	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: rs1851240471; hg19: chr9-139848323;