10-15049730-C-G

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

6
13

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]

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
OLAHNM_001039702.3 linkc.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
OLAHENST00000378228.8 linkc.128C>G p.Ala43Gly missense_variant Exon 3 of 8 1 NM_001039702.3 ENSP00000367473.4 Q9NV23-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000369
AC:
9
AN:
244224
Hom.:
0
AF XY:
0.0000227
AC XY:
3
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:
28
AN:
1456186
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
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.:
32
Alfa
AF:
0.0000307
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5
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
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
.;T;.;T;.;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.75
T;T;T;T;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.40
T;T;T;T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Uncertain
2.8
.;.;.;M;.;M
PrimateAI
Benign
0.41
T
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
D
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.

Other links and lift over

dbSNP: rs573204198; hg19: chr10-15091729; API