Genetic Variant MPRIP:p.Ser187_Ser189del (chr17-17136247-CCAGCAGCAG-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_001364716.4(MPRIP):c.560_568delGCAGCAGCA(p.Ser187_Ser189del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,555,542 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

MPRIP
NM_001364716.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.67

Publications

15 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 -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001364716.4

BP6

Variant 17-17136247-CCAGCAGCAG-C is Benign according to our data. Variant chr17-17136247-CCAGCAGCAG-C is described in ClinVar as [Benign]. Clinvar id is 2672689.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4 link	c.560_568delGCAGCAGCA	p.Ser187_Ser189del	disruptive_inframe_deletion	Exon 6 of 24	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2 link	c.560_568delGCAGCAGCA	p.Ser187_Ser189del	disruptive_inframe_deletion	Exon 6 of 24		NM_001364716.4	ENSP00000498253.1		A0A494BZV2

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

155

AN:

150558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00142

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000745

AC:

160

AN:

214846

AF XY:

0.000779

show subpopulations

Gnomad AFR exome

AF:

0.000301

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.000143

Gnomad FIN exome

AF:

0.00223

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.000383

GnomAD4 exome

AF:

0.00118

AC:

1663

AN:

1404870

Hom.:

AF XY:

0.00119

AC XY:

835

AN XY:

698924

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000403

AC:

AN:

32274

American (AMR)

AF:

0.000141

AC:

AN:

42478

Ashkenazi Jewish (ASJ)

AF:

0.000397

AC:

AN:

25196

East Asian (EAS)

AF:

0.000108

AC:

AN:

37202

South Asian (SAS)

AF:

0.000205

AC:

AN:

82820

European-Finnish (FIN)

AF:

0.00391

AC:

194

AN:

49602

Middle Eastern (MID)

AF:

0.000710

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00128

AC:

1369

AN:

1071776

Other (OTH)

AF:

0.000795

AC:

AN:

57886

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00102

AC:

154

AN:

150672

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

73550

show subpopulations

African (AFR)

AF:

0.000488

AC:

AN:

40966

American (AMR)

AF:

0.0000661

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00337

AC:

AN:

10400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00142

AC:

AN:

67626

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00173

Hom.:

3215

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MPRIP: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Mutation Taster

=179/21

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-17136247-CCAGCAGCAG-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over