Genetic Variant NM_001364716.4:c.557_568delGCAGCAGCAGCA (chr17-17136247-CCAGCAGCAGCAG-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001364716.4(MPRIP):c.557_568delGCAGCAGCAGCA(p.Ser186_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 0.00164 in 1,555,896 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

MPRIP
NM_001364716.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001364716.4

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4 link	c.557_568delGCAGCAGCAGCA	p.Ser186_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.557_568delGCAGCAGCAGCA	p.Ser186_Ser189del	disruptive_inframe_deletion	Exon 6 of 24		NM_001364716.4	ENSP00000498253.1		A0A494BZV2

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

460

AN:

150558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00250

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00339

GnomAD2 exomes

AF:

0.00152

AC:

326

AN:

214846

AF XY:

0.00140

show subpopulations

Gnomad AFR exome

AF:

0.00699

Gnomad AMR exome

AF:

0.000702

Gnomad ASJ exome

AF:

0.000224

Gnomad EAS exome

AF:

0.000642

Gnomad FIN exome

AF:

0.00238

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00149

AC:

2096

AN:

1405224

Hom.:

AF XY:

0.00150

AC XY:

1051

AN XY:

699132

show subpopulations

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

African (AFR)

AF:

0.00822

AC:

265

AN:

32256

American (AMR)

AF:

0.00101

AC:

AN:

42484

Ashkenazi Jewish (ASJ)

AF:

0.000119

AC:

AN:

25202

East Asian (EAS)

AF:

0.000374

AC:

AN:

37396

South Asian (SAS)

AF:

0.000181

AC:

AN:

82924

European-Finnish (FIN)

AF:

0.00325

AC:

161

AN:

49608

Middle Eastern (MID)

AF:

0.000355

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00140

AC:

1502

AN:

1071812

Other (OTH)

AF:

0.00157

AC:

AN:

57902

⚠️ 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: 0.391

Heterozygous variant carriers

177

265

354

442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00304

AC:

458

AN:

150672

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

239

AN XY:

73550

show subpopulations

African (AFR)

AF:

0.00640

AC:

262

AN:

40966

American (AMR)

AF:

0.00212

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000394

AC:

AN:

5078

South Asian (SAS)

AF:

0.000212

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00250

AC:

AN:

10400

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00185

AC:

125

AN:

67626

Other (OTH)

AF:

0.00383

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00271

Hom.:

3215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Mutation Taster

=193/7

polymorphism

(source)

Splicing

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

Publications

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NM_001364716.4:c.557_568delGCAGCAGCAGCA

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