rs1803916

chr12-96001026-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000895.3(LTA4H):c.1799C>G(p.Thr600Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTA4H NM_000895.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.19

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]

(HGNC:):

ACMG classification

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.1799C>G	p.Thr600Ser	missense_variant	19/19	ENST00000228740.7
LOC102723340	XR_945236.4	n.740+766G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTA4H	ENST00000228740.7	c.1799C>G	p.Thr600Ser	missense_variant	19/19	1	NM_000895.3	P1
	ENST00000551849.2	n.341+766G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.23
Sift	Benign	0.20	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.80	P;.
Vest4		0.48
MutPred		0.58		Gain of catalytic residue at M596 (P = 0.0082);.;
MVP		0.71
MPC		0.33
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.37
gMVP		0.66

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

Other links and lift over

dbSNP: rs1803916; hg19: chr12-96394804;