17-4631969-T-C

Variant names:

• chr17-4631969-T-C
• NM_001140.5:c.1729A>G

Variant summary

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

The NM_001140.5(ALOX15):​c.1729A>G​(p.Met577Val) 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. 14/22 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: ALOX15 NM_001140.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.749
• Publications: 0 publications found

Genes affected

ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ALOX15 Gene-Disease associations (from GenCC):

• pregnancy loss, recurrent, susceptibility

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=0.20163578).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001140.5. 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
	ALOX15	NM_001140.5	MANE Select	c.1729A>G	p.Met577Val	missense	Exon 13 of 14	NP_001131.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15	ENST00000293761.8	TSL:1 MANE Select	c.1729A>G	p.Met577Val	missense	Exon 13 of 14	ENSP00000293761.3	P16050-1
	ALOX15	ENST00000570836.6	TSL:2	c.1729A>G	p.Met577Val	missense	Exon 14 of 15	ENSP00000458832.1	P16050-1
	ALOX15	ENST00000574640.1	TSL:2	c.1612A>G	p.Met538Val	missense	Exon 13 of 14	ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	0.14
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.75
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.41
Sift	Benign	0.52	T
Sift4G	Benign	0.41	T
Polyphen		0.20	B
Vest4		0.11
MVP		0.71
MPC		0.19
ClinPred		0.49	T
GERP RS		4.3
Varity_R		0.25
gMVP		0.38

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: chr17-4535264;