9-27455454-G-A

Variant names:

• chr9-27455454-G-A
• rs773515192
• NM_024761.5:c.97C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024761.5(MOB3B):​c.97C>T​(p.Arg33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,100 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: MOB3B NM_024761.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• Publications: 2 publications found

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]

ENSG00000300243 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42176795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB3B	NM_024761.5	c.97C>T	p.Arg33Trp	missense_variant	Exon 2 of 4	ENST00000262244.6	NP_079037.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB3B	ENST00000262244.6	c.97C>T	p.Arg33Trp	missense_variant	Exon 2 of 4	1	NM_024761.5	ENSP00000262244.5
ENSG00000300243	ENST00000770344.1	n.149-2802G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251246 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000561 AC: 82 AN: 1461888 Hom.: 0 Cov.: 45 AF XY: 0.0000550 AC XY: 40 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000692 AC: 77 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74364

African (AFR) AF: 0.0000724 AC: 3 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000501 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97C>T (p.R33W) alteration is located in exon 2 (coding exon 1) of the MOB3B gene. This alteration results from a C to T substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a tryptophan (W). 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	0.45
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.026	D
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.55
MutPred		0.51		Loss of disorder (P = 0.0016);
MVP		0.37
MPC		0.69
ClinPred		0.73	D
GERP RS		4.0
Varity_R		0.35
gMVP		0.84
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs773515192; hg19: chr9-27455452; COSMIC: COSV51790345;