chr2-71133498-G-T

Variant summary

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

The NM_005791.3(MPHOSPH10):​c.690G>T​(p.Glu230Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,490 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MPHOSPH10
NM_005791.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15
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=0.029876053).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MPHOSPH10NM_005791.3 linkuse as main transcriptc.690G>T p.Glu230Asp missense_variant 2/11 ENST00000244230.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MPHOSPH10ENST00000244230.7 linkuse as main transcriptc.690G>T p.Glu230Asp missense_variant 2/111 NM_005791.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000399
AC:
10
AN:
250376
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135486
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.000295
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1460316
Hom.:
0
Cov.:
35
AF XY:
0.0000124
AC XY:
9
AN XY:
726568
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 08, 2023The c.690G>T (p.E230D) alteration is located in exon 2 (coding exon 2) of the MPHOSPH10 gene. This alteration results from a G to T substitution at nucleotide position 690, causing the glutamic acid (E) at amino acid position 230 to be replaced by an aspartic acid (D). 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
0.070
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.24
DANN
Benign
0.56
DEOGEN2
Benign
0.0020
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.42
T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.030
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
1.6
N;.
REVEL
Benign
0.010
Sift
Benign
0.49
T;.
Sift4G
Benign
0.64
T;T
Polyphen
0.0030
B;.
Vest4
0.12
MutPred
0.32
Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
0.30
MPC
0.11
ClinPred
0.020
T
GERP RS
-9.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.022
gMVP
0.031

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: rs777703268; hg19: chr2-71360628; API