chr8-56112973-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS1_Supporting

The NM_005372.1(MOS):c.1010A>C(p.Asp337Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,569,426 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

MOS
NM_005372.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

oocyte/zygote/embryo maturation arrest 20
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MOS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 8 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 1.1461 (below the threshold of 3.09). Trascript score misZ: 0.91545 (below the threshold of 3.09). GenCC associations: The gene is linked to oocyte/zygote/embryo maturation arrest 20.

BP4

Computational evidence support a benign effect (MetaRNN=0.10917908).

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000381 (54/1417096) while in subpopulation EAS AF = 0.000486 (19/39106). AF 95% confidence interval is 0.000317. There are 1 homozygotes in GnomAdExome4. There are 19 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005372.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOS	NM_005372.1	MANE Select	c.1010A>C	p.Asp337Ala	missense	Exon 1 of 1	NP_005363.1	P00540

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOS	ENST00000311923.1	TSL:6 MANE Select	c.1010A>C	p.Asp337Ala	missense	Exon 1 of 1	ENSP00000310722.1	P00540

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

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

GnomAD2 exomes

AF:

0.0000643

AC:

AN:

217720

AF XY:

0.0000510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000778

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000381

AC:

AN:

1417096

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

700944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31412

American (AMR)

AF:

0.00

AC:

AN:

35722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23550

East Asian (EAS)

AF:

0.000486

AC:

AN:

39106

South Asian (SAS)

AF:

0.00

AC:

AN:

79742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1091500

Other (OTH)

AF:

0.000566

AC:

AN:

58286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.11

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

0.59

PhyloP100

2.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.47

REVEL

Uncertain

0.32

Sift

Uncertain

0.010

Sift4G

Benign

0.53

Polyphen

0.21

Vest4

0.35

MutPred

0.60

Gain of MoRF binding (P = 0.0266)

MVP

0.98

MPC

1.7

ClinPred

0.10

GERP RS

5.8

Varity_R

0.046

gMVP

0.76

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over