Genetic Variant OLA1:p.Asp195Asn (chr2-174123642-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013341.5(OLA1):c.583G>A(p.Asp195Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,445,284 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: 0.0000069 ( 0 hom. )

Consequence

OLA1
NM_013341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

Variant links:

Genes affected

OLA1 (HGNC:28833): (Obg like ATPase 1) This gene encodes a member of the GTPase protein family. The encoded protein interacts with breast cancer-associated gene 1 (BRCA1) and BRCA1-associated RING domain protein (BARD1), and is involved in centrosome regulation. Overexpression of this gene has been observed in multiple types of cancer and may be associated with poor survival. Pseudogenes of this gene have been defined on chromosomes 17 and 22. [provided by RefSeq, Jun 2016]

OLA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23188487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLA1	NM_013341.5 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 6 of 11	ENST00000284719.8	NP_037473.3	Q9NTK5-1
OLA1	NM_001328688.2 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 6 of 11		NP_001315617.1
OLA1	NM_001011708.3 link	c.109G>A	p.Asp37Asn	missense_variant	Exon 5 of 10		NP_001011708.1	Q9NTK5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLA1	ENST00000284719.8 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 6 of 11	1	NM_013341.5	ENSP00000284719.3		Q9NTK5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240464

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130404

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000692

AC:

AN:

1445284

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

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:

0.00000362

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.583G>A (p.D195N) alteration is located in exon 6 (coding exon 5) of the OLA1 gene. This alteration results from a G to A substitution at nucleotide position 583, causing the aspartic acid (D) at amino acid position 195 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;.;T;T

Eigen

Benign

0.072

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

L;.;L;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

N;N;N;N;D

REVEL

Benign

0.061

Sift

Benign

0.068

T;T;T;T;D

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.015

B;B;B;.;.

Vest4

0.71

MutPred

0.44

Gain of sheet (P = 0.0011);.;Gain of sheet (P = 0.0011);.;.;

MVP

0.49

MPC

0.42

ClinPred

0.38

GERP RS

5.4

Varity_R

0.34

gMVP

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over