17-8039252-A-T

Position:

• chr17-8039252-A-T

Variant summary

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

The NM_001141.3(ALOX15B):​c.97A>T​(p.Ser33Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.97A>T	p.Ser33Cys	missense_variant	1/14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.97A>T	p.Ser33Cys	missense_variant	1/13		NP_001034219.1
ALOX15B	NM_001039131.2	c.97A>T	p.Ser33Cys	missense_variant	1/12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.97A>T	p.Ser33Cys	missense_variant	1/14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 33

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

Jan 18, 2022

The c.97A>T (p.S33C) alteration is located in exon 1 (coding exon 1) of the ALOX15B gene. This alteration results from a A to T substitution at nucleotide position 97, causing the serine (S) at amino acid position 33 to be replaced by a cysteine (C). 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	Benign	0.23
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.2	M;.;M;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.0	D;.;D;.
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;.;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.30
MutPred		0.68		Loss of disorder (P = 0.0088);Loss of disorder (P = 0.0088);Loss of disorder (P = 0.0088);Loss of disorder (P = 0.0088);
MVP		0.66
MPC		0.60
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.74
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7942570;