chr2-71133481-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005791.3(MPHOSPH10):ā€‹c.673G>Cā€‹(p.Asp225His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0645127).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MPHOSPH10NM_005791.3 linkuse as main transcriptc.673G>C p.Asp225His missense_variant 2/11 ENST00000244230.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MPHOSPH10ENST00000244230.7 linkuse as main transcriptc.673G>C p.Asp225His missense_variant 2/111 NM_005791.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151816
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.0000518
AC:
13
AN:
250814
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000377
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:
0.0000103
AC:
15
AN:
1461404
Hom.:
0
Cov.:
38
AF XY:
0.00000963
AC XY:
7
AN XY:
727046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000336
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:
0.00000659
AC:
1
AN:
151816
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74188
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
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:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 26, 2022The c.673G>C (p.D225H) alteration is located in exon 2 (coding exon 2) of the MPHOSPH10 gene. This alteration results from a G to C substitution at nucleotide position 673, causing the aspartic acid (D) at amino acid position 225 to be replaced by a histidine (H). 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
0.10
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.0089
T;T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.66
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.7
N;.
REVEL
Benign
0.12
Sift
Benign
0.036
D;.
Sift4G
Uncertain
0.025
D;D
Polyphen
0.53
P;.
Vest4
0.11
MutPred
0.32
Gain of methylation at K224 (P = 0.0662);Gain of methylation at K224 (P = 0.0662);
MVP
0.29
MPC
0.42
ClinPred
0.12
T
GERP RS
-0.30
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.036
gMVP
0.099

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: rs762085663; hg19: chr2-71360611; API