Genetic Variant NM_013341.5:c.854C>A (chr2-174081939-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013341.5(OLA1):c.854C>A(p.Ala285Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A285V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OLA1
NM_013341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.93

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034226775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLA1	NM_013341.5	MANE Select	c.854C>A	p.Ala285Glu	missense	Exon 8 of 11	NP_037473.3
OLA1	NM_001328688.2		c.791C>A	p.Ala264Glu	missense	Exon 8 of 11	NP_001315617.1
OLA1	NM_001011708.3		c.380C>A	p.Ala127Glu	missense	Exon 7 of 10	NP_001011708.1	Q9NTK5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLA1	ENST00000284719.8	TSL:1 MANE Select	c.854C>A	p.Ala285Glu	missense	Exon 8 of 11	ENSP00000284719.3	Q9NTK5-1
OLA1	ENST00000428402.6	TSL:1	c.729-6412C>A		intron	N/A	ENSP00000410385.2	Q9NTK5-3
OLA1	ENST00000409546.5	TSL:5	c.914C>A	p.Ala305Glu	missense	Exon 8 of 11	ENSP00000386350.1	J3KQ32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726276

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111282

Other (OTH)

AF:

0.00

AC:

AN:

60262

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Benign

0.092

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.070

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.81

M_CAP

Benign

0.0020

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

PhyloP100

6.9

PrimateAI

Benign

0.48

PROVEAN

Benign

3.5

REVEL

Benign

0.085

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.22

MVP

0.30

MPC

0.41

ClinPred

0.29

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.79

Mutation Taster

=61/39

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over