Variant 8-56113246-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_005372.1(MOS):c.737G>A(p.Arg246His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,552 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MOS
NM_005372.1 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

MOS (HGNC:7199): (MOS proto-oncogene, serine/threonine kinase) MOS is a serine/threonine kinase that activates the MAP kinase cascade through direct phosphorylation of the MAP kinase activator MEK (MAP2K1; MIM 176872) (Prasad et al., 2008 [PubMed 18246541]).[supplied by OMIM, Jul 2009]

MOS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.841

PP5

Variant 8-56113246-C-T is Pathogenic according to our data. Variant chr8-56113246-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2502327.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOS	NM_005372.1 linkuse as main transcript	c.737G>A	p.Arg246His	missense_variant	1/1	ENST00000311923.1	NP_005363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOS	ENST00000311923.1 linkuse as main transcript	c.737G>A	p.Arg246His	missense_variant	1/1		NM_005372.1	ENSP00000310722	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249134

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oocyte/zygote/embryo maturation arrest 20

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

0.062

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.52

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.51

MutPred

0.84

Loss of methylation at R246 (P = 0.0481);

MVP

0.96

MPC

1.7

ClinPred

0.99

GERP RS

2.0

Varity_R

0.25

gMVP

0.70

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