Variant 11-7509662-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_198474.4(OLFML1):c.683A>G(p.His228Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,250 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 0.0000066 ( 0 hom., cov: 33)

Consequence

OLFML1
NM_198474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

SYT9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OLFML1	NM_198474.4 linkuse as main transcript	c.683A>G	p.His228Arg	missense_variant	3/3	ENST00000329293.4	NP_940876.2
LOC124902806	XM_047428005.1 linkuse as main transcript	c.*1088-1479T>C		intron_variant			XP_047283961.1
OLFML1	NM_001370498.1 linkuse as main transcript	c.683A>G	p.His228Arg	missense_variant	4/4		NP_001357427.1
OLFML1	NM_001370499.1 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	3/3		NP_001357428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML1	ENST00000329293.4 linkuse as main transcript	c.683A>G	p.His228Arg	missense_variant	3/3	1	NM_198474.4	ENSP00000332511	P1
SYT9-AS1	ENST00000530201.2 linkuse as main transcript	n.1350+2461T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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:

0.00000378

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

Mar 02, 2023

The c.683A>G (p.H228R) 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 683, causing the histidine (H) at amino acid position 228 to be replaced by an arginine (R). 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

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

.;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

0.62

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

N;N

REVEL

Pathogenic

0.72

Sift

Benign

0.18

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.99

D;D

Vest4

0.35

MutPred

0.83

Gain of MoRF binding (P = 0.0492);Gain of MoRF binding (P = 0.0492);

MVP

0.81

MPC

0.12

ClinPred

0.91

GERP RS

5.7

Varity_R

0.66

gMVP

0.88

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