Variant 14-102229300-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000361847.7(MOK):c.1249G>A(p.Gly417Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G417D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MOK
ENST00000361847.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.922

Variant links:

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]

MOK links:

MOK (HGNC:):

MOK links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05797395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOK	NM_014226.3 linkuse as main transcript	c.1249G>A	p.Gly417Ser	missense_variant	12/12	ENST00000361847.7	NP_055041.1	Q9UQ07-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOK	ENST00000361847.7 linkuse as main transcript	c.1249G>A	p.Gly417Ser	missense_variant	12/12	1	NM_014226.3	ENSP00000355304.2		Q9UQ07-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453086

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1249G>A (p.G417S) alteration is located in exon 12 (coding exon 12) of the MOK gene. This alteration results from a G to A substitution at nucleotide position 1249, causing the glycine (G) at amino acid position 417 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

0.085

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.028

.;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

.;L;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.94

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.065

T;T;T

Sift4G

Benign

0.073

T;T;T

Polyphen

0.062

.;B;.

Vest4

0.054

MutPred

0.23

.;Gain of phosphorylation at G417 (P = 0.0102);.;

MVP

0.60

MPC

0.16

ClinPred

0.10

GERP RS

2.1

Varity_R

0.072

gMVP

0.027

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over