rs199545653

Variant names:

• chr17-8075670-C-G
• NM_001139.3:c.1579G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-8075670-C-G
• chr17-8075670-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001139.3(ALOX12B):​c.1579G>C​(p.Val527Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALOX12B NM_001139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12B	NM_001139.3	c.1579G>C	p.Val527Leu	missense_variant	Exon 12 of 15	ENST00000647874.1	NP_001130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.1579G>C	p.Val527Leu	missense_variant	Exon 12 of 15		NM_001139.3	ENSP00000497784.1
ALOX12B	ENST00000649809.1	c.643G>C	p.Val215Leu	missense_variant	Exon 5 of 8			ENSP00000496845.1
ALOX12B	ENST00000577351.5	n.479+505G>C		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;D;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0030	D;.;.
Sift4G	Benign	0.070	T;.;.
Polyphen		1.0	D;D;.
Vest4		0.74
MutPred		0.89		Loss of catalytic residue at V527 (P = 0.0517);Loss of catalytic residue at V527 (P = 0.0517);.;
MVP		0.88
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.65
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7978988;