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GeneBe

12-96014959-A-G

Variant summary

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

The NM_000895.3(LTA4H):c.1100T>C(p.Val367Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LTA4H
NM_000895.3 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.72
Variant links:
Genes affected
LTA4H (HGNC:6710): (leukotriene A4 hydrolase) The protein encoded by this gene is an enzyme that contains both hydrolase and aminopeptidase activities. The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. The aminopeptidase activity has been shown to degrade proline-glycine-proline (PGP), a neutrophil chemoattractant and biomarker for chronic obstructive pulmonary disease (COPD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

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=0.41453642).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LTA4HNM_000895.3 linkuse as main transcriptc.1100T>C p.Val367Ala missense_variant 12/19 ENST00000228740.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LTA4HENST00000228740.7 linkuse as main transcriptc.1100T>C p.Val367Ala missense_variant 12/191 NM_000895.3 P1P09960-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsOct 25, 2022The c.1100T>C (p.V367A) alteration is located in exon 12 (coding exon 12) of the LTA4H gene. This alteration results from a T to C substitution at nucleotide position 1100, causing the valine (V) at amino acid position 367 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.41
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.032
D;D;D
Polyphen
0.99
D;.;D
Vest4
0.45
MutPred
0.48
Gain of catalytic residue at F363 (P = 9e-04);.;.;
MVP
0.62
MPC
1.0
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.80
gMVP
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-96408737; API