chr1-46610164-C-A

Position:

• chr1-46610164-C-A

Variant summary

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

The NM_201403.3(MOB3C):​c.459G>T​(p.Lys153Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

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, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOB3C	NM_201403.3	c.459G>T	p.Lys153Asn	missense_variant	3/4	ENST00000319928.9	NP_958805.1
MOB3C	NM_145279.5	c.459G>T	p.Lys153Asn	missense_variant	3/4		NP_660322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOB3C	ENST00000319928.9	c.459G>T	p.Lys153Asn	missense_variant	3/4	2	NM_201403.3	ENSP00000315113.3
MOB3C	ENST00000271139.13	c.459G>T	p.Lys153Asn	missense_variant	3/4	1		ENSP00000271139.9
MOB3C	ENST00000371940.1	c.459G>T	p.Lys153Asn	missense_variant	2/3	1		ENSP00000361008.2
MKNK1	ENST00000531769.6	c.-171+6547G>T		intron_variant		4		ENSP00000434021.2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.615G>T (p.K205N) alteration is located in exon 3 (coding exon 3) of the MOB3C gene. This alteration results from a G to T substitution at nucleotide position 615, causing the lysine (K) at amino acid position 205 to be replaced by an asparagine (N). 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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;.
M_CAP	Benign	0.0057	T
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.5	N;D;.
REVEL	Benign	0.12
Sift	Benign	0.25	T;T;.
Sift4G	Benign	0.36	T;T;T
Polyphen		0.43	B;.;B
Vest4		0.88
MutPred		0.65		Loss of MoRF binding (P = 0.033);.;Loss of MoRF binding (P = 0.033);
MVP		0.68
MPC		0.73
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.44
gMVP		0.44

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.

Other links and lift over

hg19: chr1-47075836; COSMIC: COSV99596515;