Variant 9-136740038-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000497771.6(LCN10):c.486T>G(p.Asn162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,419,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

LCN10
ENST00000497771.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.197

Variant links:

Genes affected

LCN10 (HGNC:20892): (lipocalin 10) Members of the lipocalin family, such as LCN10, 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]

LCN10 links:

ENSG00000204003 (HGNC:):

ENSG00000204003 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038251728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN10	NM_001001712.3 linkuse as main transcript	c.486T>G	p.Asn162Lys	missense_variant	5/6	ENST00000497771.6	NP_001001712.2	Q6JVE6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LCN10	ENST00000497771.6 linkuse as main transcript	c.486T>G	p.Asn162Lys	missense_variant	5/6	1	NM_001001712.3	ENSP00000418491.1	Q6JVE6-2
ENSG00000204003	ENST00000435202.5 linkuse as main transcript	n.*483T>G		non_coding_transcript_exon_variant	10/11	2		ENSP00000399627.1	H7C1C5
ENSG00000204003	ENST00000435202.5 linkuse as main transcript	n.*483T>G		3_prime_UTR_variant	10/11	2		ENSP00000399627.1	H7C1C5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1419706

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

702450

show subpopulations

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:

0.00000367

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.486T>G (p.N162K) alteration is located in exon 5 (coding exon 5) of the LCN10 gene. This alteration results from a T to G substitution at nucleotide position 486, causing the asparagine (N) at amino acid position 162 to be replaced by a lysine (K). 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

0.31

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.6

DANN

Benign

0.56

DEOGEN2

Benign

0.00068

.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.39

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.73

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.025

B;P;B

Vest4

0.13

MutPred

0.49

.;.;Gain of methylation at N149 (P = 0.0057);

MVP

0.048

MPC

0.13

ClinPred

0.25

GERP RS

-0.26

Varity_R

0.037

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over