17-4631688-T-C

Position:

• chr17-4631688-T-C

Variant summary

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

The NM_001140.5(ALOX15):​c.1901A>G​(p.Asp634Gly) 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. 12/21 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: 3.02

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]

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=0.29902497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1901A>G	p.Asp634Gly	missense_variant	14/14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1901A>G	p.Asp634Gly	missense_variant	14/14	1	NM_001140.5	ENSP00000293761	P1
ALOX15	ENST00000570836.6	c.1901A>G	p.Asp634Gly	missense_variant	15/15	2		ENSP00000458832	P1
ALOX15	ENST00000574640.1	c.1784A>G	p.Asp595Gly	missense_variant	14/14	2		ENSP00000460483

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Dec 06, 2022

The c.1901A>G (p.D634G) alteration is located in exon 14 (coding exon 14) of the ALOX15 gene. This alteration results from a A to G substitution at nucleotide position 1901, causing the aspartic acid (D) at amino acid position 634 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;D;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.8	.;D;.
REVEL	Benign	0.16
Sift	Benign	0.098	.;T;.
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.94	P;P;.
Vest4		0.25
MVP		0.43
MPC		0.80
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.31
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr17-4534983;