rs200323689

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-136953019-C-G
• chr9-136953019-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178536.4(LCN12):​c.242C>G​(p.Ala81Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A81V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCN12 NM_178536.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21491137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN12	NM_178536.4	c.242C>G	p.Ala81Gly	missense_variant	Exon 2 of 6	ENST00000371633.8	NP_848631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN12	ENST00000371633.8	c.242C>G	p.Ala81Gly	missense_variant	Exon 2 of 6	1	NM_178536.4	ENSP00000360696.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461498 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.49	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.049
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.78	P;.
Vest4		0.35
MutPred		0.36		Loss of stability (P = 0.2329);.;
MVP		0.73
MPC		0.22
ClinPred		0.33	T
GERP RS		1.3
Varity_R		0.16
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139847471;