2-71133269-A-G

Variant names:

• chr2-71133269-A-G
• rs76328738
• NM_005791.3:c.461A>G

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.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. 15/21 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0520
• 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=0.0018321276).
• BP6: Variant 2-71133269-A-G is Benign according to our data. Variant chr2-71133269-A-G is described in ClinVar as Benign. ClinVar VariationId is 777994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 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.461A>G	p.Asn154Ser	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.461A>G	p.Asn154Ser	missense	Exon 2 of 11	ENSP00000244230.2	O00566
	MPHOSPH10	ENST00000498451.3	TSL:1	c.461A>G	p.Asn154Ser	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000857231.1		c.461A>G	p.Asn154Ser	missense	Exon 2 of 11	ENSP00000527290.1

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

GnomAD2 exomes AF: 0.00826 AC: 2078 AN: 251424 AF XY: 0.00749

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 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

African (AFR) AF: 0.0657 AC: 2198 AN: 33480

American (AMR) AF: 0.00478 AC: 214 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 33 AN: 26132

East Asian (EAS) AF: 0.00580 AC: 230 AN: 39688

South Asian (SAS) AF: 0.0125 AC: 1077 AN: 86256

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53420

Middle Eastern (MID) AF: 0.0140 AC: 81 AN: 5768

European-Non Finnish (NFE) AF: 0.00245 AC: 2726 AN: 1111998

Other (OTH) AF: 0.00959 AC: 579 AN: 60394

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

African (AFR) AF: 0.0631 AC: 2618 AN: 41498

American (AMR) AF: 0.0105 AC: 160 AN: 15278

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

East Asian (EAS) AF: 0.00984 AC: 51 AN: 5182

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

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00282 AC: 192 AN: 68002

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.00898 Hom.: 73

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

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	0.071
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.45
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.18	N
PhyloP100		-0.052
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.024
Sift	Benign	0.54	T
Sift4G	Benign	0.71	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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