Genetic Variant OLAH:p.Ala43Gly (chr10-15049730-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039702.3(OLAH):c.128C>G(p.Ala43Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,456,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

OLAH
NM_001039702.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

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]

OLAH links:

ACBD7-DCLRE1CP1 (HGNC:):

ACBD7-DCLRE1CP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40452176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLAH	NM_001039702.3 link	c.128C>G	p.Ala43Gly	missense_variant	Exon 3 of 8	ENST00000378228.8	NP_001034791.1	Q9NV23-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLAH	ENST00000378228.8 link	c.128C>G	p.Ala43Gly	missense_variant	Exon 3 of 8	1	NM_001039702.3	ENSP00000367473.4		Q9NV23-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000369

AC:

AN:

244224

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

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:

0.0000535

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1456186

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000307

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128C>G (p.A43G) alteration is located in exon 3 (coding exon 2) of the OLAH gene. This alteration results from a C to G substitution at nucleotide position 128, causing the alanine (A) at amino acid position 43 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

.;T;.;T;.;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

T;T;T;T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.40

T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.8

.;.;.;M;.;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.19

T;D;T;T;T;D

Sift4G

Benign

0.18

T;D;T;T;T;T

Polyphen

0.92, 1.0

.;.;.;P;.;D

Vest4

0.50, 0.50, 0.53

MutPred

0.65

Gain of disorder (P = 0.0425);Gain of disorder (P = 0.0425);Gain of disorder (P = 0.0425);Gain of disorder (P = 0.0425);.;Gain of disorder (P = 0.0425);

MVP

0.040

MPC

0.050

ClinPred

0.88

GERP RS

5.3

Varity_R

0.51

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over