Variant chr7-5886082-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001097622.2(OCM):c.323A>T(p.His108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,556 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

OCM
NM_001097622.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

OCM (HGNC:8105): (oncomodulin) Oncomodulin is a high-affinity calcium ion-binding protein. It belongs to the superfamily of calmodulin proteins, also known as the EF-hand proteins. Oncomodulin is an oncodevelopmental protein found in early embryonic cells in the placenta and also in tumors. [provided by RefSeq, Jul 2008]

OCM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1893745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCM	NM_001097622.2 linkuse as main transcript	c.323A>T	p.His108Leu	missense_variant	4/4	ENST00000242104.6	NP_001091091.1	P0CE72
OCM	NM_001391990.1 linkuse as main transcript	c.323A>T	p.His108Leu	missense_variant	5/5		NP_001378919.1
OCM	NM_001391991.1 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant	4/4		NP_001378920.1
OCM	XM_047420752.1 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant	4/4		XP_047276708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCM	ENST00000242104.6 linkuse as main transcript	c.323A>T	p.His108Leu	missense_variant	4/4	1	NM_001097622.2	ENSP00000242104.5		P0CE72
OCM	ENST00000416608.5 linkuse as main transcript	c.323A>T	p.His108Leu	missense_variant	5/5	5		ENSP00000401365.1		P0CE72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250980

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135758

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727104

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000935

Hom.:

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

May 27, 2022

The c.323A>T (p.H108L) alteration is located in exon 4 (coding exon 4) of the OCM gene. This alteration results from a A to T substitution at nucleotide position 323, causing the histidine (H) at amino acid position 108 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.0013

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.95

L;L

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.4

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.095

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;B

Vest4

0.20

MutPred

0.39

Gain of stability (P = 0.0061);Gain of stability (P = 0.0061);

MVP

0.70

MPC

2.0

ClinPred

0.30

GERP RS

4.2

Varity_R

0.13

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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