chr9-27455415-C-A

Position:

• chr9-27455415-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024761.5(MOB3B):​c.136G>T​(p.Ala46Ser) 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: MOB3B NM_024761.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

Genes affected

MOB3B (HGNC:23825): (MOB kinase activator 3B) The protein encoded by this gene shares similarity with the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. This gene is located on the opposite strand as the interferon kappa precursor (IFNK) gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084825695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOB3B	NM_024761.5	c.136G>T	p.Ala46Ser	missense_variant	2/4	ENST00000262244.6	NP_079037.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOB3B	ENST00000262244.6	c.136G>T	p.Ala46Ser	missense_variant	2/4	1	NM_024761.5	ENSP00000262244.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

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

Jun 05, 2024

The c.136G>T (p.A46S) alteration is located in exon 2 (coding exon 1) of the MOB3B gene. This alteration results from a G to T substitution at nucleotide position 136, causing the alanine (A) at amino acid position 46 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.65	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.034
Sift	Benign	0.58	T
Sift4G	Benign	0.70	T
Polyphen		0.0050	B
Vest4		0.32
MutPred		0.30		Gain of disorder (P = 0.023);
MVP		0.37
MPC		0.35
ClinPred		0.43	T
GERP RS		4.9
Varity_R		0.14
gMVP		0.37

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: chr9-27455413;