9-136755506-C-G

Position:

• chr9-136755506-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

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]

LCN8 (HGNC:):

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=0.219004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN8	NM_178469.4	c.237G>C	p.Glu79Asp	missense_variant	4/7	ENST00000371688.8	NP_848564.2
LCN8	NM_001345934.2	c.306G>C	p.Glu102Asp	missense_variant	4/7		NP_001332863.1
LCN8	XM_017014272.3	c.306G>C	p.Glu102Asp	missense_variant	4/6		XP_016869761.1
LCN8	XR_007061246.1	n.947G>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN8	ENST00000371688.8	c.237G>C	p.Glu79Asp	missense_variant	4/7	1	NM_178469.4	ENSP00000360753.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

The c.237G>C (p.E79D) alteration is located in exon 4 (coding exon 4) of the LCN8 gene. This alteration results from a G to C substitution at nucleotide position 237, causing the glutamic acid (E) at amino acid position 79 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.098
Sift	Benign	0.20	T;.
Sift4G	Pathogenic	0.0	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139649958;