17-7001615-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000697.3(ALOX12):c.965A>G(p.Asn322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,400 control chromosomes in the GnomAD database, including 136,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9626 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126544 hom. )

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0450

Variant links:

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 links:

ALOX12-AS1 (HGNC:):

ALOX12-AS1 links:

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

ALOX12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2104383E-4).

BP6

Variant 17-7001615-A-G is Benign according to our data. Variant chr17-7001615-A-G is described in ClinVar as [Benign]. Clinvar id is 1233269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3 link	c.965A>G	p.Asn322Ser	missense_variant	Exon 8 of 14	ENST00000251535.11	NP_000688.2	P18054
ALOX12	XM_011523780.3 link	c.758A>G	p.Asn253Ser	missense_variant	Exon 7 of 13		XP_011522082.2
ALOX12-AS1	NR_040089.1 link	n.233+8181T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11 link	c.965A>G	p.Asn322Ser	missense_variant	Exon 8 of 14	1	NM_000697.3	ENSP00000251535.6		P18054

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51617

AN:

151772

Hom.:

9622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.418

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.379

AC:

95286

AN:

251198

Hom.:

19230

AF XY:

0.392

AC XY:

53235

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.412

AC:

601532

AN:

1460510

Hom.:

126544

Cov.:

AF XY:

0.414

AC XY:

300988

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.425

Gnomad4 SAS exome

AF:

0.446

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.340

AC:

51624

AN:

151890

Hom.:

9626

Cov.:

AF XY:

0.338

AC XY:

25093

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.418

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.406

Hom.:

29147

Bravo

AF:

0.327

TwinsUK

AF:

0.426

AC:

1578

ALSPAC

AF:

0.421

AC:

1622

ESP6500AA

AF:

0.196

AC:

862

ESP6500EA

AF:

0.422

AC:

3626

ExAC

AF:

0.384

AC:

46658

Asia WGS

AF:

0.426

AC:

1478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20626912) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.5

DANN

Benign

0.67

DEOGEN2

Benign

0.15

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.28

MetaRNN

Benign

0.00022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.34

REVEL

Benign

0.13

Sift

Benign

0.62

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.014

MPC

0.22

ClinPred

0.00053

GERP RS

-4.4

Varity_R

0.20

gMVP

0.069

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over