1-46612954-T-C

Position:

chr1-46612954-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_201403.3(MOB3C):c.368A>G(p.Asp123Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,594,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MOB3C
NM_201403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

Genes affected

MOB3C (HGNC:29800): (MOB kinase activator 3C) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MOB3C links:

MKNK1 (HGNC:7110): (MAPK interacting serine/threonine kinase 1) This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]

MKNK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32816076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOB3C	NM_201403.3 linkuse as main transcript	c.368A>G	p.Asp123Gly	missense_variant	2/4	ENST00000319928.9	NP_958805.1
MOB3C	NM_145279.5 linkuse as main transcript	c.368A>G	p.Asp123Gly	missense_variant	2/4		NP_660322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MOB3C	ENST00000319928.9 linkuse as main transcript	c.368A>G	p.Asp123Gly	missense_variant	2/4	2	NM_201403.3	ENSP00000315113	P1
MOB3C	ENST00000271139.13 linkuse as main transcript	c.368A>G	p.Asp123Gly	missense_variant	2/4	1		ENSP00000271139	P1
MOB3C	ENST00000371940.1 linkuse as main transcript	c.368A>G	p.Asp123Gly	missense_variant	1/3	1		ENSP00000361008	P1
MKNK1	ENST00000531769.6 linkuse as main transcript	c.-171+3757A>G		intron_variant		4		ENSP00000434021

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238620

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000929

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441678

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000825

AC:

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

Dec 15, 2023

The c.524A>G (p.D175G) alteration is located in exon 2 (coding exon 2) of the MOB3C gene. This alteration results from a A to G substitution at nucleotide position 524, causing the aspartic acid (D) at amino acid position 175 to be replaced by a glycine (G). 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

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.8

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-5.2

D;D;.

REVEL

Uncertain

0.38

Sift

Benign

0.043

D;D;.

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.18

B;.;B

Vest4

0.70

MutPred

0.65

Loss of stability (P = 0.0671);.;Loss of stability (P = 0.0671);

MVP

0.58

MPC

0.58

ClinPred

0.77

GERP RS

5.3

Varity_R

0.70

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over