Variant 5-179796332-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000292596.15(LTC4S):c.391C>T(p.Leu131Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,487,650 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: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LTC4S
ENST00000292596.15 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.785

Variant links:

Genes affected

LTC4S (HGNC:6719): (leukotriene C4 synthase) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family includes a number of human proteins, several of which are involved the production of leukotrienes. This gene encodes an enzyme that catalyzes the first step in the biosynthesis of cysteinyl leukotrienes, potent biological compounds derived from arachidonic acid. Leukotrienes have been implicated as mediators of anaphylaxis and inflammatory conditions such as human bronchial asthma. This protein localizes to the nuclear envelope and adjacent endoplasmic reticulum. [provided by RefSeq, Jul 2008]

LTC4S links:

LTC4S (HGNC:):

LTC4S 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=0.3364678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTC4S	NM_145867.2 linkuse as main transcript	c.391C>T	p.Leu131Phe	missense_variant	5/5	ENST00000292596.15	NP_665874.1	Q16873

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTC4S	ENST00000292596.15 linkuse as main transcript	c.391C>T	p.Leu131Phe	missense_variant	5/5	1	NM_145867.2	ENSP00000292596.10		Q16873

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000457

AC:

AN:

87542

Hom.:

AF XY:

0.0000808

AC XY:

AN XY:

49528

show subpopulations

Gnomad AFR exome

AF:

0.000936

Gnomad AMR exome

AF:

0.000169

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1335530

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

658408

show subpopulations

Gnomad4 AFR exome

AF:

0.000409

Gnomad4 AMR exome

AF:

0.000136

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:

0.00000189

Gnomad4 OTH exome

AF:

0.0000901

GnomAD4 genome

AF:

0.000105

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000208

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

Jun 07, 2024

The c.391C>T (p.L131F) alteration is located in exon 5 (coding exon 5) of the LTC4S gene. This alteration results from a C to T substitution at nucleotide position 391, causing the leucine (L) at amino acid position 131 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.55

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.34

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.99

D;.

Vest4

0.25

MutPred

0.30

Loss of MoRF binding (P = 0.2294);.;

MVP

0.57

MPC

0.37

ClinPred

0.15

GERP RS

3.0

Varity_R

0.43

gMVP

0.42

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