Genetic Variant MPRIP:c.123+14693G>A (chr17-17057664-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001364716.4(MPRIP):c.123+14693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 717,724 control chromosomes in the GnomAD database, including 8,947 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 0.16 ( 2055 hom., cov: 32)

Exomes 𝑓: 0.15 ( 6892 hom. )

Consequence

MPRIP
NM_001364716.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71

Publications

20 publications found

Variant links:

Genes affected

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

MPRIP 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=0.0033490062).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4 link	c.123+14693G>A		intron_variant	Intron 1 of 23	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2 link	c.123+14693G>A		intron_variant	Intron 1 of 23		NM_001364716.4	ENSP00000498253.1		A0A494BZV2

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24402

AN:

151848

Hom.:

2052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.146

AC:

22136

AN:

151582

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.151

AC:

85622

AN:

565758

Hom.:

6892

Cov.:

AF XY:

0.151

AC XY:

45964

AN XY:

305214

show subpopulations

African (AFR)

AF:

0.184

AC:

2904

AN:

15808

American (AMR)

AF:

0.125

AC:

4334

AN:

34720

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

4547

AN:

20030

East Asian (EAS)

AF:

0.125

AC:

4006

AN:

32106

South Asian (SAS)

AF:

0.116

AC:

7266

AN:

62772

European-Finnish (FIN)

AF:

0.141

AC:

6780

AN:

48184

Middle Eastern (MID)

AF:

0.211

AC:

860

AN:

4082

European-Non Finnish (NFE)

AF:

0.156

AC:

49631

AN:

317168

Other (OTH)

AF:

0.171

AC:

5294

AN:

30888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

4059

8119

12178

16238

20297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.161

AC:

24413

AN:

151966

Hom.:

2055

Cov.:

AF XY:

0.161

AC XY:

11939

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.180

AC:

7446

AN:

41410

American (AMR)

AF:

0.160

AC:

2439

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

768

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

623

AN:

5164

South Asian (SAS)

AF:

0.107

AC:

517

AN:

4816

European-Finnish (FIN)

AF:

0.152

AC:

1600

AN:

10556

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10369

AN:

67972

Other (OTH)

AF:

0.189

AC:

397

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1016

2032

3049

4065

5081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.160

Hom.:

5881

Bravo

AF:

0.168

TwinsUK

AF:

0.157

AC:

583

ALSPAC

AF:

0.144

AC:

554

ExAC

AF:

0.134

AC:

2906

Asia WGS

AF:

0.117

AC:

410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.045

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.029

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.0

PhyloP100

-2.7

PROVEAN

Benign

-0.75

REVEL

Benign

0.014

Sift

Pathogenic

0.0

Vest4

0.015

ClinPred

0.0044

GERP RS

-1.5

Mutation Taster

=89/11

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