rs375091500

Variant names:

• chr8-56112973-T-C
• rs375091500
• NM_005372.1:c.1010A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-56112973-T-C
• chr8-56112973-T-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.1010A>G​(p.Asp337Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D337A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOS NM_005372.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• 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.1010A>G	p.Asp337Gly	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>G	p.Asp337Gly	missense	Exon 1 of 1	ENSP00000310722.1	P00540

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.8	L
PhyloP100		2.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.025	D
Sift4G	Benign	0.086	T
Polyphen		0.90	P
Vest4		0.36
MutPred		0.63		Loss of stability (P = 0.0262)
MVP		0.98
MPC		1.8
ClinPred		0.54	D
GERP RS		5.8
Varity_R		0.056
gMVP		0.81
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

dbSNP: rs375091500; hg19: chr8-57025532;