1-46613026-C-G

Variant names:

• chr1-46613026-C-G
• rs111448646
• NM_201403.3:c.296G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_201403.3(MOB3C):​c.296G>C​(p.Arg99Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOB3C NM_201403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB3C	NM_201403.3	c.296G>C	p.Arg99Pro	missense_variant	Exon 2 of 4	ENST00000319928.9	NP_958805.1
MOB3C	NM_145279.5	c.296G>C	p.Arg99Pro	missense_variant	Exon 2 of 4		NP_660322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB3C	ENST00000319928.9	c.296G>C	p.Arg99Pro	missense_variant	Exon 2 of 4	2	NM_201403.3	ENSP00000315113.3
MOB3C	ENST00000271139.13	c.296G>C	p.Arg99Pro	missense_variant	Exon 2 of 4	1		ENSP00000271139.9
MOB3C	ENST00000371940.1	c.296G>C	p.Arg99Pro	missense_variant	Exon 1 of 3	1		ENSP00000361008.2
MKNK1	ENST00000531769.6	c.-171+3685G>C		intron_variant	Intron 1 of 4	4		ENSP00000434021.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.86	D;D;.
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D;D;.
REVEL	Uncertain	0.55
Sift	Benign	0.16	T;T;.
Sift4G	Benign	0.21	T;T;T
Polyphen		0.99	D;.;D
Vest4		0.92
MutPred		0.64		Loss of MoRF binding (P = 0.0039);.;Loss of MoRF binding (P = 0.0039);
MVP		0.62
MPC		0.81
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.77
gMVP		0.89

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

Other links and lift over

dbSNP: rs111448646; hg19: chr1-47078698;