8-56113027-C-T

Variant names:

• chr8-56113027-C-T
• NM_005372.1:c.956G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_005372.1(MOS):​c.956G>A​(p.Arg319His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOS NM_005372.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-56113027-C-T is Pathogenic according to our data. Variant chr8-56113027-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2502331.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.4144519). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOS	NM_005372.1	c.956G>A	p.Arg319His	missense_variant	Exon 1 of 1	ENST00000311923.1	NP_005363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOS	ENST00000311923.1	c.956G>A	p.Arg319His	missense_variant	Exon 1 of 1	6	NM_005372.1	ENSP00000310722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Oocyte/zygote/embryo maturation arrest 20 Pathogenic:1

May 17, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.19
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.11
MutPred		0.51		Loss of MoRF binding (P = 0.0069);
MVP		0.77
MPC		1.5
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.10
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-57025586; COSMIC: COSV61336102;