2-71133269-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005791.3(MPHOSPH10):c.461A>G(p.Asn154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,614,032 control chromosomes in the GnomAD database, including 221 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (128 hom.)
• Consequence: MPHOSPH10 NM_005791.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0520

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018321276).
• BP6: Variant 2-71133269-A-G is Benign according to our data. Variant chr2-71133269-A-G is described in ClinVar as [Benign]. Clinvar id is 777994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH10	NM_005791.3	c.461A>G	p.Asn154Ser	missense_variant	2/11	ENST00000244230.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH10	ENST00000244230.7	c.461A>G	p.Asn154Ser	missense_variant	2/11	1	NM_005791.3	P1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3122 AN: 152054 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00826 AC: 2078 AN: 251424 Hom.: 50 AF XY: 0.00749 AC XY: 1018 AN XY: 135878

Gnomad AFR exome AF: 0.0655

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00805

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00489 AC: 7144 AN: 1461860 Hom.: 128 Cov.: 39 AF XY: 0.00491 AC XY: 3570 AN XY: 727228

Gnomad4 AFR exome AF: 0.0657

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.00580

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.00959

GnomAD4 genome AF: 0.0205 AC: 3124 AN: 152172 Hom.: 93 Cov.: 32 AF XY: 0.0190 AC XY: 1416 AN XY: 74394

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00582 Hom.: 29

Bravo AF: 0.0242

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.0586 AC: 258

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00944 AC: 1146

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.00425

EpiControl AF: 0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.48
Dann	Benign	0.45
DEOGEN2	Benign	0.0031	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.18	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.40	N;.
REVEL	Benign	0.024
Sift	Benign	0.54	T;.
Sift4G	Benign	0.71	T;T
Polyphen		0.0010	B;.
Vest4		0.046
MVP		0.33
MPC		0.098
ClinPred		0.0014	T
GERP RS		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs76328738; hg19: chr2-71360399; COSMIC: COSV54906396; COSMIC: COSV54906396;