17-8081161-G-C

Variant names:

• chr17-8081161-G-C
• rs72842957
• NM_001139.3:c.379C>G

Variant summary

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

The NM_001139.3(ALOX12B):​c.379C>G​(p.Pro127Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P127S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ALOX12B NM_001139.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

ENSG00000214999 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12B	NM_001139.3	c.379C>G	p.Pro127Ala	missense_variant	Exon 3 of 15	ENST00000647874.1	NP_001130.1
LOC107985075	XR_001752778.2	n.1434G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.379C>G	p.Pro127Ala	missense_variant	Exon 3 of 15		NM_001139.3	ENSP00000497784.1
ENSG00000214999	ENST00000399413.3	n.1400G>C		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251072 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461792 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727178

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;D
Eigen	Benign	0.097
Eigen_PC	Benign	-0.0065
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.042	D;.
Polyphen		0.94	P;P
Vest4		0.23
MutPred		0.49		Loss of disorder (P = 0.1234);Loss of disorder (P = 0.1234);
MVP		0.89
MPC		0.86
ClinPred		0.76	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.35

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: rs72842957; hg19: chr17-7984479;