NM_001039702.3:c.419G>A

Variant names:

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

Variant summary

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

The NM_001039702.3(OLAH):​c.419G>A​(p.Arg140His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: OLAH NM_001039702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>A	p.Arg140His	missense	Exon 6 of 8	NP_001034791.1	Q9NV23-1
	OLAH	NM_018324.3		c.578G>A	p.Arg193His	missense	Exon 7 of 9	NP_060794.1	Q9NV23-2
	ACBD7-DCLRE1CP1	NR_144471.1		n.229+5933C>T		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>A	p.Arg140His	missense	Exon 6 of 8	ENSP00000367473.4	Q9NV23-1
	OLAH	ENST00000948316.1		c.641G>A	p.Arg214His	missense	Exon 7 of 9	ENSP00000618375.1
	OLAH	ENST00000378217.3	TSL:2	c.578G>A	p.Arg193His	missense	Exon 7 of 9	ENSP00000367462.3	Q9NV23-2

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000526 AC: 13 AN: 247166 AF XY: 0.0000374

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000981

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000136 AC: 199 AN: 1458204 Hom.: 0 Cov.: 31 AF XY: 0.000127 AC XY: 92 AN XY: 725330

African (AFR) AF: 0.000120 AC: 4 AN: 33218

American (AMR) AF: 0.0000229 AC: 1 AN: 43688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000165 AC: 183 AN: 1110906

Other (OTH) AF: 0.000166 AC: 10 AN: 60244

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74420

African (AFR) AF: 0.0000482 AC: 2 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.0000982

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.086
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0020
DANN	Benign	0.47
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-4.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.024
Sift	Benign	0.047	D
Sift4G	Uncertain	0.047	D
Polyphen		0.085	B
Vest4		0.10
MVP		0.014
MPC		0.0085
ClinPred		0.040	T
GERP RS		-10
Varity_R		0.049
gMVP		0.24
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		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; COSMIC: COSV65493024; COSMIC: COSV65493024;