17-8072877-T-G

Position:

• chr17-8072877-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001139.3(ALOX12B):​c.2000A>C​(p.Gln667Pro) 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALOX12B NM_001139.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.185

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-8072877-T-G is Pathogenic according to our data. Variant chr17-8072877-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 995498.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.23295379). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	NM_001139.3	c.2000A>C	p.Gln667Pro	missense_variant	15/15	ENST00000647874.1	NP_001130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.2000A>C	p.Gln667Pro	missense_variant	15/15		NM_001139.3	ENSP00000497784.1
ALOX12B	ENST00000649809.1	c.1064A>C	p.Gln355Pro	missense_variant	8/8			ENSP00000496845.1
ALOX12B	ENST00000650441.1	n.423A>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive congenital ichthyosis 2 Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Institute for Human Genetics, University Medical Center Freiburg

Jan 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Uncertain	0.57	D;D;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	.;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;.;.
REVEL	Uncertain	0.31
Sift	Benign	0.12	T;.;.
Sift4G	Benign	0.17	T;.;.
Polyphen		0.072	B;B;.
Vest4		0.45
MutPred		0.62		Loss of MoRF binding (P = 0.0452);Loss of MoRF binding (P = 0.0452);.;
MVP		0.80
MPC		0.98
ClinPred		0.16	T
GERP RS		0.093
Varity_R		0.81
gMVP		0.91

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: rs1977009717; hg19: chr17-7976195;