Variant chr1-101825242-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058170.4(OLFM3):c.376T>G(p.Leu126Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

OLFM3
NM_058170.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

OLFM3 (HGNC:17990): (olfactomedin 3) Predicted to be involved in eye photoreceptor cell development. Predicted to be located in Golgi apparatus; extracellular space; and synapse. Predicted to be part of AMPA glutamate receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

OLFM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFM3	NM_058170.4 linkuse as main transcript	c.376T>G	p.Leu126Val	missense_variant	4/6	ENST00000370103.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFM3	ENST00000370103.9 linkuse as main transcript	c.376T>G	p.Leu126Val	missense_variant	4/6	1	NM_058170.4	P4	Q96PB7-3

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249542

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460776

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000448

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.376T>G (p.L126V) alteration is located in exon 4 (coding exon 4) of the OLFM3 gene. This alteration results from a T to G substitution at nucleotide position 376, causing the leucine (L) at amino acid position 126 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.0019

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.085

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.4

.;.;M

MutationTaster

Benign

0.89

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.64

N;N;N

REVEL

Uncertain

0.49

Sift

Benign

0.049

D;D;T

Sift4G

Uncertain

0.034

D;T;D

Polyphen

0.99

.;.;D

Vest4

0.70

MVP

0.76

MPC

1.1

ClinPred

0.61

GERP RS

-3.1

Varity_R

0.17

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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