NM_005372.1:c.1019C>G

Variant names:

• chr8-56112964-G-C
• NM_005372.1:c.1019C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_005372.1(MOS):​c.1019C>G​(p.Ser340Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOS NM_005372.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.60
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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.

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.1019C>G	p.Ser340Cys	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.1019C>G	p.Ser340Cys	missense	Exon 1 of 1	ENSP00000310722.1	P00540

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.029	D
Polyphen		0.96	D
Vest4		0.25
MutPred		0.38		Gain of catalytic residue at L341 (P = 0.0102)
MVP		0.94
MPC		1.3
ClinPred		0.79	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.54
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr8-57025523;