13-30744112-C-G

Variant names:

• chr13-30744112-C-G
• rs41351946
• NM_001629.4:c.123C>G

Variant summary

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

The NM_001629.4(ALOX5AP):​c.123C>G​(p.Ser41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S41S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALOX5AP NM_001629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001629.4. 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.123C>G	p.Ser41Arg	missense	Exon 2 of 5	NP_001620.2
	ALOX5AP	NM_001204406.2		c.294C>G	p.Ser98Arg	missense	Exon 3 of 6	NP_001191335.1	A0A087WW23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5AP	ENST00000380490.5	TSL:1 MANE Select	c.123C>G	p.Ser41Arg	missense	Exon 2 of 5	ENSP00000369858.3	P20292
	ALOX5AP	ENST00000617770.4	TSL:1	c.294C>G	p.Ser98Arg	missense	Exon 3 of 6	ENSP00000479870.1	A0A087WW23
	ALOX5AP	ENST00000892335.1		c.123C>G	p.Ser41Arg	missense	Exon 3 of 6	ENSP00000562394.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251420 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.83
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.53		Gain of catalytic residue at S41 (P = 0.0036)
MVP		0.62
MPC		0.69
ClinPred		0.70	D
GERP RS		5.7
Varity_R		0.81
gMVP		0.56
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

dbSNP: rs41351946; hg19: chr13-31318249;