chr13-30735577-C-T

Variant names:

• chr13-30735577-C-T
• ENST00000617770.4:c.143C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204406.2(ALOX5AP):​c.143C>T​(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALOX5AP NM_001204406.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740
• Publications: 0 publications found

Genes affected

ALOX5AP (HGNC:436): (arachidonate 5-lipoxygenase activating protein) This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

LOC124903146 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1270445).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204406.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	NM_001629.4	MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 5	NP_001620.2
	ALOX5AP	NM_001204406.2		c.143C>T	p.Ala48Val	missense	Exon 2 of 6	NP_001191335.1	A0A087WW23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	ENST00000617770.4	TSL:1	c.143C>T	p.Ala48Val	missense	Exon 2 of 6	ENSP00000479870.1	A0A087WW23
	ALOX5AP	ENST00000380490.5	TSL:1 MANE Select	c.-29C>T		5_prime_UTR	Exon 1 of 5	ENSP00000369858.3	P20292
	ALOX5AP	ENST00000892335.1		c.-29C>T		5_prime_UTR	Exon 2 of 6	ENSP00000562394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.72
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.13	T
PhyloP100		-0.074
PrimateAI	Benign	0.27	T
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MVP		0.25
GERP RS		5.0
PromoterAI		-0.22	Neutral
gMVP		0.061
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

hg19: chr13-31309714;