10-15049653-C-A

Variant summary

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

The NM_001039702.3(OLAH):​c.51C>A​(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,589,776 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

OLAH
NM_001039702.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.292
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=0.30510435).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OLAHNM_001039702.3 linkc.51C>A p.Asn17Lys 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.51C>A p.Asn17Lys missense_variant Exon 3 of 8 1 NM_001039702.3 ENSP00000367473.4 Q9NV23-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000866
AC:
2
AN:
230820
Hom.:
0
AF XY:
0.00000799
AC XY:
1
AN XY:
125160
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000585
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000918
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000487
AC:
7
AN:
1437598
Hom.:
0
Cov.:
29
AF XY:
0.00000560
AC XY:
4
AN XY:
714372
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000453
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.51C>A (p.N17K) alteration is located in exon 3 (coding exon 2) of the OLAH gene. This alteration results from a C to A substitution at nucleotide position 51, causing the asparagine (N) at amino acid position 17 to be replaced by a lysine (K). 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
Pathogenic
0.62
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.096
.;T;.;T;.;.
Eigen
Benign
0.14
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.62
T;T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.31
T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Uncertain
2.7
.;.;.;M;.;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.6
D;D;D;D;D;D
REVEL
Benign
0.16
Sift
Uncertain
0.023
D;D;D;D;T;D
Sift4G
Benign
0.22
T;D;T;D;D;D
Polyphen
0.92, 1.0
.;.;.;P;.;D
Vest4
0.48, 0.47, 0.48
MutPred
0.52
Gain of methylation at N17 (P = 5e-04);Gain of methylation at N17 (P = 5e-04);Gain of methylation at N17 (P = 5e-04);Gain of methylation at N17 (P = 5e-04);.;Gain of methylation at N17 (P = 5e-04);
MVP
0.040
MPC
0.050
ClinPred
0.95
D
GERP RS
5.3
Varity_R
0.20
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs770598766; hg19: chr10-15091652; API