4-70958988-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173468.4(MOB1B):c.129G>A(p.Met43Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: MOB1B NM_173468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

Genes affected

MOB1B (HGNC:29801): (MOB kinase activator 1B) 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. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

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=0.3103147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOB1B	NM_173468.4	c.129G>A	p.Met43Ile	missense_variant	2/6	ENST00000309395.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOB1B	ENST00000309395.7	c.129G>A	p.Met43Ile	missense_variant	2/6	1	NM_173468.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251408 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Feb 23, 2023

The c.129G>A (p.M43I) alteration is located in exon 2 (coding exon 2) of the MOB1B gene. This alteration results from a G to A substitution at nucleotide position 129, causing the methionine (M) at amino acid position 43 to be replaced by an isoleucine (I). 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	Uncertain	0.40
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	0.053
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0080	.;B;.
Vest4		0.59, 0.59
MutPred		0.28		.;Loss of disorder (P = 0.1074);.;
MVP		0.70
MPC		0.14
ClinPred		0.33	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.53

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: rs1302388497; hg19: chr4-71824705;