9-136755303-C-G

Variant names:

• chr9-136755303-C-G
• NM_178469.4:c.362G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178469.4(LCN8):​c.362G>C​(p.Gly121Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,288 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LCN8 NM_178469.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28792965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN8	NM_178469.4	c.362G>C	p.Gly121Ala	missense_variant	Exon 5 of 7	ENST00000371688.8	NP_848564.2
LCN8	NM_001345934.2	c.431G>C	p.Gly144Ala	missense_variant	Exon 5 of 7		NP_001332863.1
LCN8	XM_017014272.3	c.431G>C	p.Gly144Ala	missense_variant	Exon 5 of 6		XP_016869761.1
LCN8	XR_007061246.1	n.1072G>C		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN8	ENST00000371688.8	c.362G>C	p.Gly121Ala	missense_variant	Exon 5 of 7	1	NM_178469.4	ENSP00000360753.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458288 Hom.: 0 Cov.: 64 AF XY: 0.00000413 AC XY: 3 AN XY: 725694

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362G>C (p.G121A) alteration is located in exon 5 (coding exon 5) of the LCN8 gene. This alteration results from a G to C substitution at nucleotide position 362, causing the glycine (G) at amino acid position 121 to be replaced by an alanine (A). 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	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0030	.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.16
Sift	Benign	0.21	T;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.42
MutPred		0.56		Loss of ubiquitination at K124 (P = 0.1037);.;
MVP		0.26
MPC		0.67
ClinPred		0.33	T
GERP RS		2.7
Varity_R		0.085
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-139649755;