Genetic Variant MPHOSPH10:p.Ile234Thr (chr2-71133509-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005791.3(MPHOSPH10):c.701T>C(p.Ile234Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000881 in 1,611,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I234N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82

Publications

2 publications found

Variant links:

Genes affected

MPHOSPH10 (HGNC:7213): (M-phase phosphoprotein 10) This gene encodes a protein that is phosphorylated during mitosis. The protein localizes to the nucleolus during interphase and to the chromosomes during M phase. The protein associates with the U3 small nucleolar ribonucleoprotein 60-80S complexes and may be involved in pre-rRNA processing. [provided by RefSeq, Dec 2010]

MPHOSPH10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016037136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	NM_005791.3	MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 2 of 11	NP_005782.1	O00566

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPHOSPH10	ENST00000244230.7	TSL:1 MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 2 of 11	ENSP00000244230.2	O00566
MPHOSPH10	ENST00000498451.3	TSL:1	c.701T>C	p.Ile234Thr	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
MPHOSPH10	ENST00000857231.1		c.701T>C	p.Ile234Thr	missense	Exon 2 of 11	ENSP00000527290.1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

248844

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000548

AC:

AN:

1459474

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

726180

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33220

American (AMR)

AF:

0.000159

AC:

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26030

East Asian (EAS)

AF:

0.000101

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

85934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1111148

Other (OTH)

AF:

0.000133

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000407

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41554

American (AMR)

AF:

0.000458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000807

Hom.:

Bravo

AF:

0.000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.0086

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

PhyloP100

5.8

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.18

Sift

Benign

0.21

Sift4G

Uncertain

0.0040

Polyphen

0.80

Vest4

0.29

MVP

0.36

MPC

0.50

ClinPred

0.13

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.081

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over