9-135663365-C-G

Variant names:

• chr9-135663365-C-G
• rs560303340
• NM_001393661.1:c.44C>G

Variant summary

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

The NM_001393661.1(LCN9):​c.44C>G​(p.Ala15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. A15S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LCN9 NM_001393661.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

LCN9 (HGNC:17442): (lipocalin 9) Members of the lipocalin family, such as LCN9, 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

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=0.22706926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393661.1. 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
	LCN9	NM_001393661.1	MANE Select	c.44C>G	p.Ala15Gly	missense	Exon 1 of 6	NP_001380590.1	Q8WX39-2
	LCN9	NR_171893.1		n.57C>G		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN9	ENST00000619315.2	TSL:1 MANE Select	c.44C>G	p.Ala15Gly	missense	Exon 1 of 6	ENSP00000482296.2	Q8WX39-2
	LCN9	ENST00000277526.8	TSL:5	n.44C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000277526.4	A0AAA9WZE8
	LCN9	ENST00000430290.6	TSL:5	n.30C>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.35	T
Polyphen		0.94	P
Vest4		0.39
MutPred		0.63		Loss of stability (P = 0.0519)
MVP		0.014
MPC		0.22
ClinPred		0.57	D
GERP RS		1.6
PromoterAI		-0.026	Neutral
Varity_R		0.19
gMVP		0.63
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs560303340; hg19: chr9-138555211;