17-6998570-A-C

Variant names:

• chr17-6998570-A-C
• rs148602792
• NM_000697.3:c.399A>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000697.3(ALOX12):​c.399A>C​(p.Lys133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,613,986 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00080 (7 hom.)
• Consequence: ALOX12 NM_000697.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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:):

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004290968).
• BP6: Variant 17-6998570-A-C is Benign according to our data. Variant chr17-6998570-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3256964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12	NM_000697.3	c.399A>C	p.Lys133Asn	missense_variant	Exon 3 of 14	ENST00000251535.11	NP_000688.2
ALOX12	XM_011523780.3	c.399A>C	p.Lys133Asn	missense_variant	Exon 3 of 13		XP_011522082.2
ALOX12-AS1	NR_040089.1	n.233+11226T>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.399A>C	p.Lys133Asn	missense_variant	Exon 3 of 14	1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152182 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00140 AC: 352 AN: 251072 Hom.: 2 AF XY: 0.00144 AC XY: 195 AN XY: 135844

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000520

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000804 AC: 1175 AN: 1461686 Hom.: 7 Cov.: 31 AF XY: 0.000829 AC XY: 603 AN XY: 727158

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.000827 AC: 126 AN: 152300 Hom.: 0 Cov.: 31 AF XY: 0.000739 AC XY: 55 AN XY: 74456

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00176 Hom.: 2

Bravo AF: 0.000876

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00106 AC: 129

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ALOX12: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.0043	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.099
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.66	P;.
Vest4		0.34
MutPred		0.54		Loss of ubiquitination at K133 (P = 0.0199);.;
MVP		0.42
MPC		0.61
ClinPred		0.042	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.19
gMVP		0.63

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

Other links and lift over

dbSNP: rs148602792; hg19: chr17-6901889;