Variant 9-136741938-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001712.3(LCN10):c.200C>T(p.Ala67Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

LCN10
NM_001001712.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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:

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ACMG classification

Classification made for transcript

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=0.28510553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN10	NM_001001712.3 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	2/6	ENST00000497771.6	NP_001001712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN10	ENST00000497771.6 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	2/6	1	NM_001001712.3	ENSP00000418491	A2	Q6JVE6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244516

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459054

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.00000824

AC:

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

Dec 03, 2021

The c.200C>T (p.A67V) alteration is located in exon 2 (coding exon 2) of the LCN10 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

.;.;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.83

T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.66

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.068

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.38

MutPred

0.31

Loss of disorder (P = 0.0963);Loss of disorder (P = 0.0963);Loss of disorder (P = 0.0963);

MVP

0.28

MPC

0.40

ClinPred

0.97

GERP RS

3.4

Varity_R

0.16

gMVP

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over