dbSNP rs2303267: MPHOSPH6:p.Ile58Val (chr16-82151507-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005792.2(MPHOSPH6):c.172A>G(p.Ile58Val) variant causes a missense change. The variant allele was found at a frequency of 0.0311 in 1,585,124 control chromosomes in the GnomAD database, including 942 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 82 hom., cov: 33)

Exomes 𝑓: 0.032 ( 860 hom. )

Consequence

MPHOSPH6
NM_005792.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.32

Publications

15 publications found

Variant links:

Genes affected

MPHOSPH6 (HGNC:7214): (M-phase phosphoprotein 6) Predicted to enable RNA binding activity. Involved in maturation of 5.8S rRNA. Located in cytosol; nucleolus; and nucleoplasm. Colocalizes with nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

MPHOSPH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030200183).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH6	NM_005792.2 link	c.172A>G	p.Ile58Val	missense_variant	Exon 3 of 5	ENST00000258169.9	NP_005783.2
MPHOSPH6	XM_011522808.4 link	c.118A>G	p.Ile40Val	missense_variant	Exon 4 of 6		XP_011521110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH6	ENST00000258169.9 link	c.172A>G	p.Ile58Val	missense_variant	Exon 3 of 5	1	NM_005792.2	ENSP00000258169.4

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3960

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.0496

Gnomad SAS

AF:

0.0597

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0368

AC:

8536

AN:

232116

AF XY:

0.0375

show subpopulations

Gnomad AFR exome

AF:

0.00551

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.0319

Gnomad EAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.0421

Gnomad NFE exome

AF:

0.0322

Gnomad OTH exome

AF:

0.0354

GnomAD4 exome

AF:

0.0316

AC:

45273

AN:

1432850

Hom.:

860

Cov.:

AF XY:

0.0326

AC XY:

23161

AN XY:

711064

show subpopulations

African (AFR)

AF:

0.00436

AC:

140

AN:

32092

American (AMR)

AF:

0.0432

AC:

1692

AN:

39174

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

707

AN:

24990

East Asian (EAS)

AF:

0.0507

AC:

1993

AN:

39324

South Asian (SAS)

AF:

0.0550

AC:

4399

AN:

79958

European-Finnish (FIN)

AF:

0.0409

AC:

2150

AN:

52596

Middle Eastern (MID)

AF:

0.0272

AC:

145

AN:

5332

European-Non Finnish (NFE)

AF:

0.0293

AC:

32293

AN:

1100302

Other (OTH)

AF:

0.0297

AC:

1754

AN:

59082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2065

4130

6196

8261

10326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1222

2444

3666

4888

6110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0260

AC:

3964

AN:

152274

Hom.:

Cov.:

AF XY:

0.0271

AC XY:

2020

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00611

AC:

254

AN:

41556

American (AMR)

AF:

0.0274

AC:

419

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3468

East Asian (EAS)

AF:

0.0497

AC:

258

AN:

5192

South Asian (SAS)

AF:

0.0599

AC:

289

AN:

4822

European-Finnish (FIN)

AF:

0.0421

AC:

446

AN:

10596

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0313

AC:

2129

AN:

68026

Other (OTH)

AF:

0.0265

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

193

386

580

773

966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0288

Hom.:

206

Bravo

AF:

0.0234

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00705

AC:

ESP6500EA

AF:

0.0313

AC:

268

ExAC

AF:

0.0370

AC:

4494

Asia WGS

AF:

0.0540

AC:

186

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0056

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;D

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.

PhyloP100

6.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.10

Sift

Benign

0.17

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.91

P;.

Vest4

0.43

MPC

0.0055

ClinPred

0.031

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.24

Mutation Taster

=84/16

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over