17-8072865-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001139.3(ALOX12B):c.2012A>G(p.Gln671Arg) 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. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALOX12B NM_001139.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

ALOX12B (HGNC:430): (arachidonate 12-lipoxygenase, 12R type) This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22595653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12B	NM_001139.3	c.2012A>G	p.Gln671Arg	missense_variant	15/15	ENST00000647874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12B	ENST00000647874.1	c.2012A>G	p.Gln671Arg	missense_variant	15/15		NM_001139.3	P1
ALOX12B	ENST00000649809.1	c.1076A>G	p.Gln359Arg	missense_variant	8/8
ALOX12B	ENST00000650441.1	n.435A>G		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.2012A>G (p.Q671R) alteration is located in exon 15 (coding exon 15) of the ALOX12B gene. This alteration results from a A to G substitution at nucleotide position 2012, causing the glutamine (Q) at amino acid position 671 to be replaced by an arginine (R). 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	0.079
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.35	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;.;.
REVEL	Benign	0.19
Sift	Benign	0.16	T;.;.
Sift4G	Benign	0.11	T;.;.
Polyphen		0.0050	B;B;.
Vest4		0.22
MutPred		0.50		Gain of MoRF binding (P = 0.0269);Gain of MoRF binding (P = 0.0269);.;
MVP		0.78
MPC		0.78
ClinPred		0.18	T
GERP RS		3.8
Varity_R		0.34
gMVP		0.57

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: chr17-7976183;