NM_001039702.3:c.280C>G

Variant names:

• chr10-15061840-C-G
• rs768895645
• NM_001039702.3:c.280C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001039702.3(OLAH):​c.280C>G​(p.Pro94Ala) 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 pathogenic outcome for this variant. 12/21 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)
• Consequence: OLAH NM_001039702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

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.280C>G	p.Pro94Ala	missense	Exon 4 of 8	NP_001034791.1	Q9NV23-1
	OLAH	NM_018324.3		c.439C>G	p.Pro147Ala	missense	Exon 5 of 9	NP_060794.1	Q9NV23-2
	ACBD7-DCLRE1CP1	NR_144471.1		n.229+9693G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLAH	ENST00000378228.8	TSL:1 MANE Select	c.280C>G	p.Pro94Ala	missense	Exon 4 of 8	ENSP00000367473.4	Q9NV23-1
	OLAH	ENST00000948316.1		c.502C>G	p.Pro168Ala	missense	Exon 5 of 9	ENSP00000618375.1
	OLAH	ENST00000378217.3	TSL:2	c.439C>G	p.Pro147Ala	missense	Exon 5 of 9	ENSP00000367462.3	Q9NV23-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0053	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.13
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.14
Sift	Benign	0.15	T
Sift4G	Benign	0.076	T
Polyphen		0.63	P
Vest4		0.23
MutPred		0.94		Loss of methylation at K93 (P = 0.082)
MVP		0.014
MPC		0.0091
ClinPred		0.86	D
GERP RS		-0.84
Varity_R		0.064
gMVP		0.45
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs768895645; hg19: chr10-15103839;