Genetic Variant MOB1A:p.Thr120Ser (chr2-74165268-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_018221.5(MOB1A):c.359C>G(p.Thr120Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000508 in 1,574,608 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: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MOB1A
NM_018221.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

Variant links:

Genes affected

MOB1A (HGNC:16015): (MOB kinase activator 1A) The protein encoded by this gene is a component of the Hippo signaling pathway, which controls organ size and tumor growth by enhancing apoptosis. Loss of the encoded protein results in cell proliferation and cancer formation. The encoded protein is also involved in the control of microtubule stability during cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

MOB1A links:

Genome browser will be placed here

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=0.28987348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB1A	NM_018221.5 link	c.359C>G	p.Thr120Ser	missense_variant	Exon 4 of 6	ENST00000396049.5	NP_060691.2	Q9H8S9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MOB1A	ENST00000396049.5 link	c.359C>G	p.Thr120Ser	missense_variant	Exon 4 of 6	1	NM_018221.5	ENSP00000379364.3	Q9H8S9-1
MOB1A	ENST00000463975.1 link	n.553C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
MOB1A	ENST00000495286.5 link	n.545C>G		non_coding_transcript_exon_variant	Exon 4 of 5	3
MOB1A	ENST00000497054.5 link	n.548C>G		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000146

AC:

AN:

206124

Hom.:

AF XY:

0.00000902

AC XY:

AN XY:

110838

show subpopulations

Gnomad AFR exome

AF:

0.0000779

Gnomad AMR exome

AF:

0.0000698

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1422408

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

704634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.0000505

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000830

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359C>G (p.T120S) alteration is located in exon 4 (coding exon 4) of the MOB1A gene. This alteration results from a C to G substitution at nucleotide position 359, causing the threonine (T) at amino acid position 120 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

0.26

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0049

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.32

Sift

Benign

0.25

Sift4G

Benign

0.63

Polyphen

0.029

Vest4

0.61

MutPred

0.50

Gain of phosphorylation at Y117 (P = 0.2466);

MVP

0.43

MPC

0.62

ClinPred

0.13

GERP RS

5.2

Varity_R

0.49

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over