8-56112964-G-C

Position:

• chr8-56112964-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOS	NM_005372.1	c.1019C>G	p.Ser340Cys	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	c.1019C>G	p.Ser340Cys	missense_variant	1/1	6	NM_005372.1	ENSP00000310722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.1019C>G (p.S340C) alteration is located in exon 1 (coding exon 1) of the MOS gene. This alteration results from a C to G substitution at nucleotide position 1019, causing the serine (S) at amino acid position 340 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-57025523;