chr12-96003014-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000895.3(LTA4H):c.1664C>T(p.Ala555Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000741 in 1,605,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 0 hom. )
Consequence
LTA4H
NM_000895.3 missense
NM_000895.3 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 9.35
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTA4H | NM_000895.3 | c.1664C>T | p.Ala555Val | missense_variant | 18/19 | ENST00000228740.7 | |
LOC102723340 | XR_945236.4 | n.740+2754G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTA4H | ENST00000228740.7 | c.1664C>T | p.Ala555Val | missense_variant | 18/19 | 1 | NM_000895.3 | P1 | |
ENST00000551849.2 | n.341+2754G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152164Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000755 AC: 18AN: 238302Hom.: 0 AF XY: 0.0000858 AC XY: 11AN XY: 128242
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GnomAD4 exome AF: 0.0000716 AC: 104AN: 1453488Hom.: 0 Cov.: 30 AF XY: 0.0000762 AC XY: 55AN XY: 722008
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74336
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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 | Jan 23, 2024 | The c.1664C>T (p.A555V) alteration is located in exon 18 (coding exon 18) of the LTA4H gene. This alteration results from a C to T substitution at nucleotide position 1664, causing the alanine (A) at amino acid position 555 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at