chr10-15065600-G-T

Variant names:

• chr10-15065600-G-T
• rs145059634
• NM_001039702.3:c.419G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039702.3(OLAH):​c.419G>T​(p.Arg140Leu) 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. 15/23 in silico tools predict a benign outcome for this variant. 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. R140H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLAH NM_001039702.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09
• Publications: 8 publications found

Genes affected

OLAH (HGNC:25625): (oleoyl-ACP hydrolase) Enables dodecanoyl-[acyl-carrier-protein] hydrolase activity; myristoyl-[acyl-carrier-protein] hydrolase activity; and palmitoyl-[acyl-carrier-protein] hydrolase activity. Involved in medium-chain fatty acid biosynthetic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299798 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039702.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLAH	NM_001039702.3	MANE Select	c.419G>T	p.Arg140Leu	missense	Exon 6 of 8	NP_001034791.1	Q9NV23-1
	OLAH	NM_018324.3		c.578G>T	p.Arg193Leu	missense	Exon 7 of 9	NP_060794.1	Q9NV23-2
	ACBD7-DCLRE1CP1	NR_144471.1		n.229+5933C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLAH	ENST00000378228.8	TSL:1 MANE Select	c.419G>T	p.Arg140Leu	missense	Exon 6 of 8	ENSP00000367473.4	Q9NV23-1
	OLAH	ENST00000948316.1		c.641G>T	p.Arg214Leu	missense	Exon 7 of 9	ENSP00000618375.1
	OLAH	ENST00000378217.3	TSL:2	c.578G>T	p.Arg193Leu	missense	Exon 7 of 9	ENSP00000367462.3	Q9NV23-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0010
DANN	Benign	0.47
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-4.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Benign	0.17	T
Sift4G	Benign	0.070	T
Polyphen		0.072	B
Vest4		0.11
MutPred		0.60		Gain of ubiquitination at K136 (P = 0.0527)
MVP		0.014
MPC		0.0096
ClinPred		0.32	T
GERP RS		-10
Varity_R		0.12
gMVP		0.30
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.31		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs145059634; hg19: chr10-15107599;