9-136755506-C-G

Variant names:

• chr9-136755506-C-G
• NM_178469.4:c.237G>C

Variant summary

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

The NM_178469.4(LCN8):​c.237G>C​(p.Glu79Asp) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: LCN8 NM_178469.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.428
• Publications: 0 publications found

Genes affected

LCN8 (HGNC:27038): (lipocalin 8) Members of the lipocalin family, such as LCN8, 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=0.219004).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178469.4. 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
	LCN8	NM_178469.4	MANE Select	c.237G>C	p.Glu79Asp	missense	Exon 4 of 7	NP_848564.2
	LCN8	NM_001345934.2		c.306G>C	p.Glu102Asp	missense	Exon 4 of 7	NP_001332863.1	Q6JVE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN8	ENST00000371688.8	TSL:1 MANE Select	c.237G>C	p.Glu79Asp	missense	Exon 4 of 7	ENSP00000360753.3	Q6JVE9-2
	LCN8	ENST00000612714.1	TSL:1	c.306G>C	p.Glu102Asp	missense	Exon 4 of 7	ENSP00000482512.1	Q6JVE9-1
	LCN8	ENST00000479767.1	TSL:1	n.635G>C		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 34

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0072	T
Eigen	Benign	0.053
Eigen_PC	Benign	-0.0074
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.43
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.098
Sift	Benign	0.20	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.27
MutPred		0.48		Loss of sheet (P = 0.1158)
MVP		0.44
MPC		0.52
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.44
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr9-139649958;