Genetic Variant NM_001364716.4:c.3277G>A (chr17-17164868-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_001364716.4(MPRIP):c.3277G>A(p.Val1093Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,304,052 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0061 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

MPRIP
NM_001364716.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.502

Publications

10 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.063).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00614 (935/152384) while in subpopulation AFR AF = 0.0213 (887/41592). AF 95% confidence interval is 0.0202. There are 15 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4 link	c.3277G>A	p.Val1093Met	missense_variant	Exon 16 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.3277G>A	p.Val1093Met	missense_variant	Exon 16 of 24		NM_001364716.4	ENSP00000498253.1		A0A494BZV2

Frequencies

GnomAD3 genomes

AF:

0.00611

AC:

931

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00122

AC:

179

AN:

146860

AF XY:

0.000935

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000587

AC:

676

AN:

1151668

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

288

AN XY:

564688

show subpopulations

African (AFR)

AF:

0.0228

AC:

556

AN:

24412

American (AMR)

AF:

0.000920

AC:

AN:

28258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15934

East Asian (EAS)

AF:

0.00

AC:

AN:

12844

South Asian (SAS)

AF:

0.000171

AC:

AN:

76160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27178

Middle Eastern (MID)

AF:

0.000909

AC:

AN:

4402

European-Non Finnish (NFE)

AF:

0.0000239

AC:

AN:

920866

Other (OTH)

AF:

0.00132

AC:

AN:

41614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00614

AC:

935

AN:

152384

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0213

AC:

887

AN:

41592

American (AMR)

AF:

0.00229

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68042

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00385

Hom.:

Bravo

AF:

0.00684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.7

(source)

DANN

Benign

0.80

PhyloP100

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

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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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