17-8044935-C-A

Position:

• chr17-8044935-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001141.3(ALOX15B):​c.783C>A​(p.Phe261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.114

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2988997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.783C>A	p.Phe261Leu	missense_variant	6/14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.783C>A	p.Phe261Leu	missense_variant	6/13		NP_001034219.1
ALOX15B	NM_001039131.2	c.783C>A	p.Phe261Leu	missense_variant	6/12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.783C>A	p.Phe261Leu	missense_variant	6/14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461886 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.783C>A (p.F261L) alteration is located in exon 6 (coding exon 6) of the ALOX15B gene. This alteration results from a C to A substitution at nucleotide position 783, causing the phenylalanine (F) at amino acid position 261 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;D;.;.
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.3	L;.;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.0	D;.;D;.
REVEL	Uncertain	0.38
Sift	Benign	0.24	T;.;T;.
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.55	P;.;P;P
Vest4		0.20
MutPred		0.62		Loss of methylation at K259 (P = 0.1719);Loss of methylation at K259 (P = 0.1719);Loss of methylation at K259 (P = 0.1719);Loss of methylation at K259 (P = 0.1719);
MVP		0.84
MPC		0.69
ClinPred		0.97	D
GERP RS		2.0
Varity_R		0.69
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7948253;