chr14-102229566-A-C

Variant names:

• chr14-102229566-A-C
• rs950904649
• NM_014226.3:c.1073T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014226.3(MOK):​c.1073T>G​(p.Val358Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOK NM_014226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

Genes affected

MOK (HGNC:9833): (MOK protein kinase) This gene belongs to the MAP kinase superfamily. The gene was found to be regulated by caudal type transcription factor 2 (Cdx2) protein. The encoded protein, which is localized to epithelial cells in the intestinal crypt, may play a role in growth arrest and differentiation of cells of upper crypt and lower villus regions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06567767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014226.3. 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
	MOK	NM_014226.3	MANE Select	c.1073T>G	p.Val358Gly	missense	Exon 11 of 12	NP_055041.1	Q9UQ07-1
	MOK	NM_001330234.2		c.1070T>G	p.Val357Gly	missense	Exon 11 of 12	NP_001317163.1	Q9UQ07-6
	MOK	NM_001272011.2		c.983T>G	p.Val328Gly	missense	Exon 10 of 11	NP_001258940.1	Q9UQ07-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOK	ENST00000361847.7	TSL:1 MANE Select	c.1073T>G	p.Val358Gly	missense	Exon 11 of 12	ENSP00000355304.2	Q9UQ07-1
	MOK	ENST00000517966.5	TSL:1	c.156T>G	p.Gly52Gly	synonymous	Exon 5 of 6	ENSP00000453224.1	H0YKX6
	MOK	ENST00000523231.5	TSL:1	c.156T>G	p.Gly52Gly	synonymous	Exon 4 of 5	ENSP00000453762.1	H0YKX6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.061
PhyloP100		1.6
Varity_R		0.048
gMVP		0.15
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs950904649; hg19: chr14-102695903;