11-77102924-G-A

Position:

chr11-77102924-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006189.1(OMP):c.85G>A(p.Val29Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

OMP
NM_006189.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

OMP (HGNC:8136): (olfactory marker protein) Olfactory marker protein is uniquely associated with the mature olfactory receptor neurons in many vertebrate species from fish to man. The OMP gene structure and protein sequence are highly conserved between mouse, rat and human. Results of the mouse knockout studies show that OMP-null mice are compromised in their ability to respond to odor stimuli, and that OMP represents a novel modulatory component of the odor detection/signal transduction cascade. [provided by RefSeq, Jul 2008]

OMP links:

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040327936).

BP6

Variant 11-77102924-G-A is Benign according to our data. Variant chr11-77102924-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3204316.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OMP	NM_006189.1 linkuse as main transcript	c.85G>A	p.Val29Met	missense_variant	1/1	ENST00000529803.1
CAPN5	NM_004055.5 linkuse as main transcript	c.297+9111G>A		intron_variant		ENST00000648180.1
CAPN5	XM_011545225.1 linkuse as main transcript	c.417+9111G>A		intron_variant
CAPN5	XM_017018223.3 linkuse as main transcript	c.405+9111G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMP	ENST00000529803.1 linkuse as main transcript	c.85G>A	p.Val29Met	missense_variant	1/1		NM_006189.1	P1
CAPN5	ENST00000648180.1 linkuse as main transcript	c.297+9111G>A		intron_variant			NM_004055.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000729

AC:

AN:

246896

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134568

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.0000580

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:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1460528

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726554

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000381

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74528

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.000709

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.30

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

M_CAP

Benign

0.018

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.079

Sift

Benign

0.051

Sift4G

Benign

0.074

Polyphen

0.051

Vest4

0.28

MVP

0.014

MPC

0.14

ClinPred

0.030

GERP RS

1.3

Varity_R

0.085

gMVP

0.39

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