1-46610100-T-G

Variant summary

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

The NM_201403.3(MOB3C):​c.523A>C​(p.Ser175Arg) 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. 13/20 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

MOB3C
NM_201403.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
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]
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]

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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=0.4190286).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MOB3CNM_201403.3 linkuse as main transcriptc.523A>C p.Ser175Arg missense_variant 3/4 ENST00000319928.9 NP_958805.1
MOB3CNM_145279.5 linkuse as main transcriptc.523A>C p.Ser175Arg missense_variant 3/4 NP_660322.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MOB3CENST00000319928.9 linkuse as main transcriptc.523A>C p.Ser175Arg missense_variant 3/42 NM_201403.3 ENSP00000315113 P1
MOB3CENST00000271139.13 linkuse as main transcriptc.523A>C p.Ser175Arg missense_variant 3/41 ENSP00000271139 P1
MOB3CENST00000371940.1 linkuse as main transcriptc.523A>C p.Ser175Arg missense_variant 2/31 ENSP00000361008 P1
MKNK1ENST00000531769.6 linkuse as main transcriptc.-171+6611A>C intron_variant 4 ENSP00000434021

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsApr 08, 2024The c.679A>C (p.S227R) alteration is located in exon 3 (coding exon 3) of the MOB3C gene. This alteration results from a A to C substitution at nucleotide position 679, causing the serine (S) at amino acid position 227 to be replaced by an arginine (R). 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
0.28
BayesDel_addAF
Benign
-0.014
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.086
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.83
T;T;.
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.8
L;.;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.8
N;N;.
REVEL
Benign
0.085
Sift
Benign
0.26
T;T;.
Sift4G
Benign
0.25
T;T;T
Polyphen
0.091
B;.;B
Vest4
0.60
MutPred
0.31
Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);
MVP
0.37
MPC
0.60
ClinPred
0.31
T
GERP RS
1.4
Varity_R
0.081
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr1-47075772; API