chr10-15049660-T-C

Variant names:

• chr10-15049660-T-C
• rs1168382909
• NM_001039702.3:c.58T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039702.3(OLAH):​c.58T>C​(p.Tyr20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLAH NM_001039702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358
• Publications: 1 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]

ACBD7-DCLRE1CP1 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18723398).

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.58T>C	p.Tyr20His	missense	Exon 3 of 8	NP_001034791.1	Q9NV23-1
	OLAH	NM_018324.3		c.58T>C	p.Tyr20His	missense	Exon 3 of 9	NP_060794.1	Q9NV23-2
	ACBD7-DCLRE1CP1	NR_144471.1		n.229+21873A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLAH	ENST00000378228.8	TSL:1 MANE Select	c.58T>C	p.Tyr20His	missense	Exon 3 of 8	ENSP00000367473.4	Q9NV23-1
	OLAH	ENST00000948316.1		c.121T>C	p.Tyr41His	missense	Exon 3 of 9	ENSP00000618375.1
	OLAH	ENST00000378217.3	TSL:2	c.58T>C	p.Tyr20His	missense	Exon 3 of 9	ENSP00000367462.3	Q9NV23-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000418 AC: 1 AN: 239246 AF XY: 0.00000771

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000336

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: 0.00000138 AC: 2 AN: 1448218 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2 AN XY: 720312

African (AFR) AF: 0.00 AC: 0 AN: 32674

American (AMR) AF: 0.0000250 AC: 1 AN: 39940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 83306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107928

Other (OTH) AF: 0.00 AC: 0 AN: 59990

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.36
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.33	B
Vest4		0.34
MutPred		0.48		Gain of methylation at K21 (P = 0.0514)
MVP		0.040
MPC		0.017
ClinPred		0.53	D
GERP RS		5.3
Varity_R		0.18
gMVP		0.14
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1168382909; hg19: chr10-15091659; COSMIC: COSV100984858; COSMIC: COSV100984858;