Variant 11-7509905-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198474.4(OLFML1):c.926A>G(p.Asp309Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OLFML1
NM_198474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

Variant links:

Genes affected

OLFML1 (HGNC:24473): (olfactomedin like 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

OLFML1 links:

LOC124902806 (HGNC:):

LOC124902806 links:

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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	Protein	UniProt
OLFML1	NM_198474.4 linkuse as main transcript	c.926A>G	p.Asp309Gly	missense_variant	3/3	ENST00000329293.4	NP_940876.2	Q6UWY5Q5HYE3
OLFML1	NM_001370498.1 linkuse as main transcript	c.926A>G	p.Asp309Gly	missense_variant	4/4		NP_001357427.1
OLFML1	NM_001370499.1 linkuse as main transcript	c.518A>G	p.Asp173Gly	missense_variant	3/3		NP_001357428.1
LOC124902806	XM_047428005.1 linkuse as main transcript	c.*1088-1722T>C		intron_variant			XP_047283961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML1	ENST00000329293.4 linkuse as main transcript	c.926A>G	p.Asp309Gly	missense_variant	3/3	1	NM_198474.4	ENSP00000332511.3		Q6UWY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251408

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135904

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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 18, 2024

The c.926A>G (p.D309G) alteration is located in exon 3 (coding exon 3) of the OLFML1 gene. This alteration results from a A to G substitution at nucleotide position 926, causing the aspartic acid (D) at amino acid position 309 to be replaced by a glycine (G). 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

0.23

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.70

P;P

Vest4

0.63

MutPred

0.58

Loss of disorder (P = 0.1713);Loss of disorder (P = 0.1713);

MVP

0.83

MPC

0.079

ClinPred

0.98

GERP RS

3.1

Varity_R

0.90

gMVP

0.71

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