10-15073184-C-G

Variant names:

• chr10-15073184-C-G
• NM_001039702.3:c.753C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039702.3(OLAH):​c.753C>G​(p.Asn251Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OLAH NM_001039702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06572881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLAH	NM_001039702.3	c.753C>G	p.Asn251Lys	missense_variant	Exon 8 of 8	ENST00000378228.8	NP_001034791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLAH	ENST00000378228.8	c.753C>G	p.Asn251Lys	missense_variant	Exon 8 of 8	1	NM_001039702.3	ENSP00000367473.4
OLAH	ENST00000378217.3	c.912C>G	p.Asn304Lys	missense_variant	Exon 9 of 9	2		ENSP00000367462.3
OLAH	ENST00000485251.1	n.314C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.912C>G (p.N304K) alteration is located in exon 9 (coding exon 8) of the OLAH gene. This alteration results from a C to G substitution at nucleotide position 912, causing the asparagine (N) at amino acid position 304 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	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.24
DANN	Benign	0.68
DEOGEN2	Benign	0.0071	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.096
Sift	Benign	0.60	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.042	B;P
Vest4		0.069
MutPred		0.50		Loss of ubiquitination at K255 (P = 0.0525);.;
MVP		0.014
MPC		0.019
ClinPred		0.29	T
GERP RS		0.18
Varity_R		0.26
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-15115183;