Variant chr2-71134050-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005791.3(MPHOSPH10):c.871A>G(p.Lys291Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,608,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.591

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0051208436).

BP6

Variant 2-71134050-A-G is Benign according to our data. Variant chr2-71134050-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2208587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH10	NM_005791.3 linkuse as main transcript	c.871A>G	p.Lys291Glu	missense_variant	3/11	ENST00000244230.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH10	ENST00000244230.7 linkuse as main transcript	c.871A>G	p.Lys291Glu	missense_variant	3/11	1	NM_005791.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000684

AC:

104

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.000523

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:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000522

AC:

130

AN:

249188

Hom.:

AF XY:

0.000534

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000972

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.00113

AC:

1649

AN:

1456672

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

801

AN XY:

724822

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.000881

GnomAD4 genome

AF:

0.000684

AC:

104

AN:

152148

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000486

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.66

DANN

Benign

0.81

DEOGEN2

Benign

0.0038

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.00082

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.20

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.051

Sift

Benign

1.0

T;.

Sift4G

Benign

0.99

T;T

Polyphen

0.0

B;.

Vest4

0.073

MVP

0.43

MPC

0.17

ClinPred

0.0085

GERP RS

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.047

gMVP

0.033

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