Genetic Variant NM_005791.3:c.719T>C (chr2-71133527-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005791.3(MPHOSPH10):c.719T>C(p.Ile240Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00139 in 1,610,850 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 13 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.83

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031051338).

BP6

Variant 2-71133527-T-C is Benign according to our data. Variant chr2-71133527-T-C is described in ClinVar as Benign. ClinVar VariationId is 784986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00743 (1132/152266) while in subpopulation AFR AF = 0.0249 (1036/41538). AF 95% confidence interval is 0.0237. There are 8 homozygotes in GnomAd4. There are 525 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

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.719T>C	p.Ile240Thr	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.719T>C	p.Ile240Thr	missense	Exon 2 of 11	ENSP00000244230.2	O00566
MPHOSPH10	ENST00000498451.3	TSL:1	c.719T>C	p.Ile240Thr	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
MPHOSPH10	ENST00000857231.1		c.719T>C	p.Ile240Thr	missense	Exon 2 of 11	ENSP00000527290.1

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

1132

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00182

AC:

450

AN:

247886

AF XY:

0.00144

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000889

Gnomad OTH exome

AF:

0.000837

GnomAD4 exome

AF:

0.000762

AC:

1111

AN:

1458584

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

472

AN XY:

725734

show subpopulations

African (AFR)

AF:

0.0259

AC:

858

AN:

33148

American (AMR)

AF:

0.00146

AC:

AN:

43944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1110922

Other (OTH)

AF:

0.00183

AC:

110

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00743

AC:

1132

AN:

152266

Hom.:

Cov.:

AF XY:

0.00705

AC XY:

525

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0249

AC:

1036

AN:

41538

American (AMR)

AF:

0.00484

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00603

Hom.:

Bravo

AF:

0.00857

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00211

AC:

256

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

0.026

Eigen_PC

Benign

0.041

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

PhyloP100

5.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.3

REVEL

Benign

0.23

Sift

Benign

0.048

Sift4G

Benign

0.11

Polyphen

0.55

Vest4

0.094

MVP

0.27

MPC

0.16

ClinPred

0.060

GERP RS

4.9

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.076

gMVP

0.039

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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