17-6998520-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000697.3(ALOX12):c.349G>C(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,590 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: ALOX12 NM_000697.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24

Genes affected

ALOX12 (HGNC:429): (arachidonate 12-lipoxygenase, 12S type) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00692302).
• BP6: Variant 17-6998520-G-C is Benign according to our data. Variant chr17-6998520-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647316.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.349G>C	p.Gly117Arg	missense_variant	3/14	ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.233+11276C>G		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.349G>C	p.Gly117Arg	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.349G>C	p.Gly117Arg	missense_variant	3/14	1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+13676C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 152188 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000399 AC: 100 AN: 250528 Hom.: 0 AF XY: 0.000347 AC XY: 47 AN XY: 135548

Gnomad AFR exome AF: 0.00385

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000177 AC: 259 AN: 1461284 Hom.: 2 Cov.: 31 AF XY: 0.000155 AC XY: 113 AN XY: 726870

Gnomad4 AFR exome AF: 0.00394

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152306 Hom.: 1 Cov.: 31 AF XY: 0.00101 AC XY: 75 AN XY: 74478

Gnomad4 AFR AF: 0.00383

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000345 Hom.: 0

Bravo AF: 0.00137

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

ALOX12: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	21
Dann	Benign	0.91
DEOGEN2	Benign	0.096	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0069	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.83	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.15	N;.
REVEL	Benign	0.056
Sift	Benign	0.57	T;.
Sift4G	Benign	0.67	T;T
Polyphen		0.0010	B;.
Vest4		0.42
MutPred		0.41		Gain of catalytic residue at G117 (P = 0.0879);.;
MVP		0.47
MPC		0.33
ClinPred		0.0086	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145526271; hg19: chr17-6901839;