chr14-102229522-C-A

Variant names:

• chr14-102229522-C-A
• rs370862359
• NM_014226.3:c.1117G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014226.3(MOK):​c.1117G>T​(p.Gly373*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MOK NM_014226.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1117G>T	p.Gly373*	stop_gained	Exon 11 of 12	NP_055041.1	Q9UQ07-1
	MOK	NM_001330234.2		c.1114G>T	p.Gly372*	stop_gained	Exon 11 of 12	NP_001317163.1	Q9UQ07-6
	MOK	NM_001272011.2		c.1027G>T	p.Gly343*	stop_gained	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.1117G>T	p.Gly373*	stop_gained	Exon 11 of 12	ENSP00000355304.2	Q9UQ07-1
	MOK	ENST00000517966.5	TSL:1	c.200G>T	p.Trp67Leu	missense	Exon 5 of 6	ENSP00000453224.1	H0YKX6
	MOK	ENST00000523231.5	TSL:1	c.200G>T	p.Trp67Leu	missense	Exon 4 of 5	ENSP00000453762.1	H0YKX6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	33
DANN	Benign	0.95
Eigen	Uncertain	0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.12	N
PhyloP100		0.097
Vest4		0.77
ClinPred		0.82	D
GERP RS		2.0
Mutation Taster		=53/147	disease causing (fs/PTC)

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

dbSNP: rs370862359; hg19: chr14-102695859;