chr2-71133151-C-T

Variant summary

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

The NM_005791.3(MPHOSPH10):​c.343C>T​(p.Arg115Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,978 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.521
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]

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=0.007317841).
BP6
Variant 2-71133151-C-T is Benign according to our data. Variant chr2-71133151-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3201895.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MPHOSPH10NM_005791.3 linkuse as main transcriptc.343C>T p.Arg115Cys missense_variant 2/11 ENST00000244230.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MPHOSPH10ENST00000244230.7 linkuse as main transcriptc.343C>T p.Arg115Cys missense_variant 2/111 NM_005791.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00104
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000103
AC:
26
AN:
251296
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000513
AC:
75
AN:
1461808
Hom.:
1
Cov.:
36
AF XY:
0.0000454
AC XY:
33
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.000986
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000302
AC:
46
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.00104
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000105
Hom.:
0
Bravo
AF:
0.000351
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsFeb 11, 2022This 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
0.057
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
8.5
DANN
Benign
0.81
DEOGEN2
Benign
0.0027
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0090
N
LIST_S2
Benign
0.17
T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.0073
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.7
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.080
N;.
REVEL
Benign
0.018
Sift
Benign
0.057
T;.
Sift4G
Benign
0.068
T;T
Polyphen
0.0
B;.
Vest4
0.096
MVP
0.18
MPC
0.17
ClinPred
0.030
T
GERP RS
-1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.044
gMVP
0.052

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.

Other links and lift over

dbSNP: rs141436611; hg19: chr2-71360281; COSMIC: COSV99731358; COSMIC: COSV99731358; API