chr2-71132930-C-A

Variant names:

• chr2-71132930-C-A
• rs138723053
• NM_005791.3:c.122C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005791.3(MPHOSPH10):​c.122C>A​(p.Ser41Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,610,868 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (91 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (126 hom.)
• Consequence: MPHOSPH10 NM_005791.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.90
• Publications: 7 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=0.0029021204).
• BP6: Variant 2-71132930-C-A is Benign according to our data. Variant chr2-71132930-C-A is described in ClinVar as Benign. ClinVar VariationId is 777993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

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.122C>A	p.Ser41Tyr	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.122C>A	p.Ser41Tyr	missense	Exon 2 of 11	ENSP00000244230.2	O00566
	MPHOSPH10	ENST00000498451.3	TSL:1	c.122C>A	p.Ser41Tyr	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000857231.1		c.122C>A	p.Ser41Tyr	missense	Exon 2 of 11	ENSP00000527290.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3121 AN: 152100 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00980

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.0162

GnomAD2 exomes AF: 0.00805 AC: 1999 AN: 248250 AF XY: 0.00744

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00796

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00476 AC: 6937 AN: 1458650 Hom.: 126 Cov.: 31 AF XY: 0.00479 AC XY: 3474 AN XY: 725290

African (AFR) AF: 0.0642 AC: 2132 AN: 33198

American (AMR) AF: 0.00473 AC: 210 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 33 AN: 26070

East Asian (EAS) AF: 0.00575 AC: 228 AN: 39646

South Asian (SAS) AF: 0.0124 AC: 1062 AN: 85914

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53340

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5750

European-Non Finnish (NFE) AF: 0.00236 AC: 2625 AN: 1110078

Other (OTH) AF: 0.00931 AC: 561 AN: 60240

GnomAD4 genome AF: 0.0205 AC: 3123 AN: 152218 Hom.: 91 Cov.: 32 AF XY: 0.0190 AC XY: 1417 AN XY: 74418

African (AFR) AF: 0.0630 AC: 2616 AN: 41506

American (AMR) AF: 0.0105 AC: 161 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5190

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00282 AC: 192 AN: 68020

Other (OTH) AF: 0.0161 AC: 34 AN: 2116

Alfa AF: 0.0101 Hom.: 24

Bravo AF: 0.0242

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.0524 AC: 226

ESP6500EA AF: 0.00281 AC: 24

ExAC AF: 0.00902 AC: 1093

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00326

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	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.0067
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.9
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.43	T
Sift4G	Uncertain	0.025	D
Polyphen		0.015	B
Vest4		0.23
MVP		0.34
MPC		0.21
ClinPred		0.022	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.46
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs138723053; hg19: chr2-71360060; COSMIC: COSV54906388; COSMIC: COSV54906388;