Genetic Variant NM_001039702.3:c.516T>A (chr10-15065697-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001039702.3(OLAH):c.516T>A(p.Phe172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OLAH
NM_001039702.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150

Publications

0 publications found

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:

ENSG00000299798 (HGNC:):

ENSG00000299798 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047941834).

BP6

Variant 10-15065697-T-A is Benign according to our data. Variant chr10-15065697-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2323040.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLAH	NM_001039702.3	MANE Select	c.516T>A	p.Phe172Leu	missense	Exon 6 of 8	NP_001034791.1	Q9NV23-1
OLAH	NM_018324.3		c.675T>A	p.Phe225Leu	missense	Exon 7 of 9	NP_060794.1	Q9NV23-2
ACBD7-DCLRE1CP1	NR_144471.1		n.229+5836A>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLAH	ENST00000378228.8	TSL:1 MANE Select	c.516T>A	p.Phe172Leu	missense	Exon 6 of 8	ENSP00000367473.4	Q9NV23-1
OLAH	ENST00000948316.1		c.738T>A	p.Phe246Leu	missense	Exon 7 of 9	ENSP00000618375.1
OLAH	ENST00000378217.3	TSL:2	c.675T>A	p.Phe225Leu	missense	Exon 7 of 9	ENSP00000367462.3	Q9NV23-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251274

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.69

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.29

M_CAP

Benign

0.0026

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.2

PhyloP100

-0.015

PrimateAI

Benign

0.35

PROVEAN

Benign

1.1

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.084

MutPred

0.63

Loss of methylation at K170 (P = 0.0891)

MVP

0.014

MPC

0.0082

ClinPred

0.077

GERP RS

-0.19

Varity_R

0.11

gMVP

0.33

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over