Genetic Variant MRNIP:p.Arg154Gly (chr5-179840949-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016175.4(MRNIP):c.460A>G(p.Arg154Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,603,424 control chromosomes in the GnomAD database, including 430,849 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.79 ( 48216 hom., cov: 30)

Exomes 𝑓: 0.72 ( 382633 hom. )

Consequence

MRNIP
NM_016175.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

Publications

40 publications found

Variant links:

Genes affected

MRNIP (HGNC:30817): (MRN complex interacting protein) Enables chromatin binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of double-strand break repair; and response to ionizing radiation. Located in nucleoplasm. Colocalizes with Mre11 complex. [provided by Alliance of Genome Resources, Apr 2022]

MRNIP 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=7.785444E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRNIP	NM_016175.4 link	c.460A>G	p.Arg154Gly	missense_variant	Exon 6 of 7	ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3 link	c.295A>G	p.Arg99Gly	missense_variant	Exon 4 of 5		NP_001017987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11 link	c.460A>G	p.Arg154Gly	missense_variant	Exon 6 of 7	1	NM_016175.4	ENSP00000292586.6

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120092

AN:

151872

Hom.:

48163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.777

GnomAD2 exomes

AF:

0.772

AC:

181956

AN:

235568

AF XY:

0.763

show subpopulations

Gnomad AFR exome

AF:

0.921

Gnomad AMR exome

AF:

0.875

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.911

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.751

GnomAD4 exome

AF:

0.724

AC:

1050118

AN:

1451436

Hom.:

382633

Cov.:

AF XY:

0.724

AC XY:

522476

AN XY:

721366

show subpopulations

African (AFR)

AF:

0.928

AC:

30935

AN:

33330

American (AMR)

AF:

0.869

AC:

38285

AN:

44078

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

19227

AN:

25886

East Asian (EAS)

AF:

0.919

AC:

36243

AN:

39452

South Asian (SAS)

AF:

0.765

AC:

64851

AN:

84742

European-Finnish (FIN)

AF:

0.756

AC:

39446

AN:

52198

Middle Eastern (MID)

AF:

0.762

AC:

3993

AN:

5240

European-Non Finnish (NFE)

AF:

0.698

AC:

772724

AN:

1106622

Other (OTH)

AF:

0.742

AC:

44414

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

13586

27173

40759

54346

67932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19670

39340

59010

78680

98350

<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:

0.791

AC:

120204

AN:

151988

Hom.:

48216

Cov.:

AF XY:

0.795

AC XY:

59050

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.917

AC:

38022

AN:

41476

American (AMR)

AF:

0.829

AC:

12665

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2611

AN:

3466

East Asian (EAS)

AF:

0.906

AC:

4645

AN:

5128

South Asian (SAS)

AF:

0.780

AC:

3757

AN:

4814

European-Finnish (FIN)

AF:

0.753

AC:

7959

AN:

10568

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.707

AC:

48008

AN:

67936

Other (OTH)

AF:

0.779

AC:

1647

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1218

2436

3654

4872

6090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.729

Hom.:

171943

Bravo

AF:

0.801

TwinsUK

AF:

0.694

AC:

2575

ALSPAC

AF:

0.689

AC:

2656

ESP6500AA

AF:

0.909

AC:

4006

ESP6500EA

AF:

0.706

AC:

6075

ExAC

AF:

0.758

AC:

91617

Asia WGS

AF:

0.858

AC:

2984

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.013

T;T;.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

MetaRNN

Benign

7.8e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.61

PROVEAN

Benign

-0.69

N;N;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.29

T;T;T;T;T;T

Sift4G

Benign

0.27

T;T;D;T;D;T

Polyphen

0.0

B;B;.;.;.;B

Vest4

0.024

MPC

0.084

ClinPred

0.0043

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.051

gMVP

0.069

Mutation Taster

=100/0

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