Genetic Variant MPRIP:p.Ser2Trp (chr17-17042853-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001364716.4(MPRIP):c.5C>G(p.Ser2Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,561,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

MPRIP
NM_001364716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3828681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4 link	c.5C>G	p.Ser2Trp	missense_variant	Exon 1 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.5C>G	p.Ser2Trp	missense_variant	Exon 1 of 24		NM_001364716.4	ENSP00000498253.1		A0A494BZV2

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

196670

AF XY:

0.0000185

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000351

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1410586

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

700244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31054

American (AMR)

AF:

0.00

AC:

AN:

39318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24858

East Asian (EAS)

AF:

0.00

AC:

AN:

34906

South Asian (SAS)

AF:

0.00

AC:

AN:

81812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3990

European-Non Finnish (NFE)

AF:

0.0000276

AC:

AN:

1087438

Other (OTH)

AF:

0.0000173

AC:

AN:

57702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151196

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41350

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

67638

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000837

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.5C>G (p.S2W) alteration is located in exon 1 (coding exon 1) of the MPRIP gene. This alteration results from a C to G substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.057

.;T;.;T

Eigen

Benign

0.090

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

.;.;L;L

PhyloP100

4.2

PROVEAN

Uncertain

-3.1

.;D;N;N

REVEL

Benign

0.094

Sift

Uncertain

0.0020

.;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.90, 0.95

.;.;P;P

Vest4

0.46, 0.48, 0.44

MutPred

0.26

Loss of phosphorylation at S2 (P = 0.0312);Loss of phosphorylation at S2 (P = 0.0312);Loss of phosphorylation at S2 (P = 0.0312);Loss of phosphorylation at S2 (P = 0.0312);

MVP

0.18

MPC

2.5

ClinPred

0.74

GERP RS

2.3

PromoterAI

-0.35

Neutral

(source)

Varity_R

0.16

gMVP

0.68

Mutation Taster

=71/29

polymorphism

(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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17-17042853-C-G

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