Variant 11-7509788-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198474.4(OLFML1):c.809T>C(p.Ile270Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

OLFML1
NM_198474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML1	NM_198474.4 linkuse as main transcript	c.809T>C	p.Ile270Thr	missense_variant	3/3	ENST00000329293.4	NP_940876.2	Q6UWY5Q5HYE3
OLFML1	NM_001370498.1 linkuse as main transcript	c.809T>C	p.Ile270Thr	missense_variant	4/4		NP_001357427.1
OLFML1	NM_001370499.1 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	3/3		NP_001357428.1
LOC124902806	XM_047428005.1 linkuse as main transcript	c.*1088-1605A>G		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.809T>C	p.Ile270Thr	missense_variant	3/3	1	NM_198474.4	ENSP00000332511.3		Q6UWY5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00000795

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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

Bravo

AF:

0.0000151

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

Feb 06, 2024

The c.809T>C (p.I270T) alteration is located in exon 3 (coding exon 3) of the OLFML1 gene. This alteration results from a T to C substitution at nucleotide position 809, causing the isoleucine (I) at amino acid position 270 to be replaced by a threonine (T). 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

0.32

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;D

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

.;T

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Pathogenic

0.89

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.1

D;D

REVEL

Pathogenic

0.92

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.92

P;P

Vest4

0.88

MutPred

0.89

Loss of stability (P = 0.0013);Loss of stability (P = 0.0013);

MVP

0.95

MPC

0.15

ClinPred

0.99

GERP RS

5.7

Varity_R

0.66

gMVP

0.78

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