NM_005791.3:c.418G>A

Variant names:

• chr2-71133226-G-A
• rs10175940
• NM_005791.3:c.418G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.08
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 775729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	NM_005791.3	MANE Select	c.418G>A	p.Asp140Asn	missense	Exon 2 of 11	NP_005782.1	O00566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	ENST00000244230.7	TSL:1 MANE Select	c.418G>A	p.Asp140Asn	missense	Exon 2 of 11	ENSP00000244230.2	O00566
	MPHOSPH10	ENST00000498451.3	TSL:1	c.418G>A	p.Asp140Asn	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000857231.1		c.418G>A	p.Asp140Asn	missense	Exon 2 of 11	ENSP00000527290.1

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

GnomAD2 exomes AF: 0.00329 AC: 828 AN: 251298 AF XY: 0.00246

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 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

African (AFR) AF: 0.0414 AC: 1387 AN: 33480

American (AMR) AF: 0.00322 AC: 144 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.000197 AC: 219 AN: 1111990

Other (OTH) AF: 0.00386 AC: 233 AN: 60394

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

African (AFR) AF: 0.0427 AC: 1773 AN: 41566

American (AMR) AF: 0.00798 AC: 122 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68036

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00521 Hom.: 37

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.050
Sift	Benign	0.15	T
Sift4G	Benign	0.29	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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

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