14-102231788-T-A

Position:

• chr14-102231788-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014226.3(MOK):​c.900A>T​(p.Arg300Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOK NM_014226.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092054754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOK	NM_014226.3	c.900A>T	p.Arg300Ser	missense_variant	10/12	ENST00000361847.7	NP_055041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOK	ENST00000361847.7	c.900A>T	p.Arg300Ser	missense_variant	10/12	1	NM_014226.3	ENSP00000355304	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 25, 2023

The c.900A>T (p.R300S) alteration is located in exon 10 (coding exon 10) of the MOK gene. This alteration results from a A to T substitution at nucleotide position 900, causing the arginine (R) at amino acid position 300 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.0
DANN	Benign	0.86
DEOGEN2	Benign	0.0047	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.15	T;T;T
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.014	.;B;.
Vest4		0.20
MutPred		0.32		.;Gain of glycosylation at R300 (P = 0.0216);.;
MVP		0.47
MPC		0.16
ClinPred		0.26	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.29

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: chr14-102698125;