1-46612925-C-T

Variant names:

• chr1-46612925-C-T
• rs779328921
• NM_201403.3:c.397G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201403.3(MOB3C):​c.397G>A​(p.Glu133Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E133Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOB3C NM_201403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15230846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201403.3. 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
	MOB3C	NM_201403.3	MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 2 of 4	NP_958805.1	Q70IA8
	MOB3C	NM_145279.5		c.397G>A	p.Glu133Lys	missense	Exon 2 of 4	NP_660322.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOB3C	ENST00000319928.9	TSL:2 MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 2 of 4	ENSP00000315113.3	Q70IA8
	MOB3C	ENST00000271139.13	TSL:1	c.397G>A	p.Glu133Lys	missense	Exon 2 of 4	ENSP00000271139.9	Q70IA8
	MOB3C	ENST00000371940.1	TSL:1	c.397G>A	p.Glu133Lys	missense	Exon 1 of 3	ENSP00000361008.2	Q70IA8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		3.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.064
Sift	Benign	0.71	T
Sift4G	Benign	0.92	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.39		Gain of ubiquitination at E133 (P = 0.0131)
MVP		0.47
MPC		0.47
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.31
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs779328921; hg19: chr1-47078597;