2-71133226-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005791.3(MPHOSPH10):c.418G>A(p.Asp140Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,614,142 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (40 hom.)
• Consequence: MPHOSPH10 NM_005791.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08

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=0.0026017427).
• BP6: Variant 2-71133226-G-A is Benign according to our data. Variant chr2-71133226-G-A is described in ClinVar as [Benign]. Clinvar id is 775729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1930/152300) while in subpopulation AFR AF= 0.0427 (1773/41566). AF 95% confidence interval is 0.041. There are 35 homozygotes in gnomad4. There are 930 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH10	NM_005791.3	c.418G>A	p.Asp140Asn	missense_variant	2/11	ENST00000244230.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH10	ENST00000244230.7	c.418G>A	p.Asp140Asn	missense_variant	2/11	1	NM_005791.3	P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1921 AN: 152182 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00329 AC: 828 AN: 251298 Hom.: 13 AF XY: 0.00246 AC XY: 334 AN XY: 135816

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.00272

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: 0.000370

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00138 AC: 2024 AN: 1461842 Hom.: 40 Cov.: 39 AF XY: 0.00121 AC XY: 879 AN XY: 727220

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.00322

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152300 Hom.: 35 Cov.: 32 AF XY: 0.0125 AC XY: 930 AN XY: 74464

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00260 Hom.: 12

Bravo AF: 0.0148

ESP6500AA AF: 0.0404 AC: 178

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00404 AC: 490

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000474

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0082	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.050
Sift	Benign	0.15	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.081	B;.
Vest4		0.059
MVP		0.52
MPC		0.12
ClinPred		0.0098	T
GERP RS		3.2
Varity_R		0.023
gMVP		0.13

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

Other links and lift over

dbSNP: rs10175940; hg19: chr2-71360356; COSMIC: COSV99071343; COSMIC: COSV99071343;