Variant 6-89674555-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014611.3(MDN1):c.12796A>G(p.Arg4266Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,590,582 control chromosomes in the GnomAD database, including 1,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 124 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1676 hom. )

Consequence

MDN1
NM_014611.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

MDN1 (HGNC:18302): (midasin AAA ATPase 1) Predicted to enable ATP binding activity. Involved in ribosomal large subunit assembly. Located in cytosol; intermediate filament cytoskeleton; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

MDN1 links:

MDN1 (HGNC:):

MDN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019529164).

BP6

Variant 6-89674555-T-C is Benign according to our data. Variant chr6-89674555-T-C is described in ClinVar as [Benign]. Clinvar id is 403078.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDN1	NM_014611.3 linkuse as main transcript	c.12796A>G	p.Arg4266Gly	missense_variant	79/102	ENST00000369393.8	NP_055426.1	Q9NU22
MDN1-AS1	NR_111915.1 linkuse as main transcript	n.106-841T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8 linkuse as main transcript	c.12796A>G	p.Arg4266Gly	missense_variant	79/102	1	NM_014611.3	ENSP00000358400.3		Q9NU22

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5248

AN:

152212

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0490

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.0397

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0332

Gnomad OTH

AF:

0.0372

GnomAD3 exomes

AF:

0.0508

AC:

11536

AN:

227120

Hom.:

449

AF XY:

0.0540

AC XY:

6731

AN XY:

124564

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.0612

Gnomad ASJ exome

AF:

0.0318

Gnomad EAS exome

AF:

0.0413

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0353

Gnomad OTH exome

AF:

0.0519

GnomAD4 exome

AF:

0.0396

AC:

56893

AN:

1438252

Hom.:

1676

Cov.:

AF XY:

0.0421

AC XY:

30098

AN XY:

714606

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.0585

Gnomad4 ASJ exome

AF:

0.0321

Gnomad4 EAS exome

AF:

0.0291

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0291

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0345

AC:

5252

AN:

152330

Hom.:

124

Cov.:

AF XY:

0.0368

AC XY:

2739

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.0489

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.0392

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.0332

Gnomad4 OTH

AF:

0.0406

Alfa

AF:

0.0350

Hom.:

145

Bravo

AF:

0.0351

TwinsUK

AF:

0.0402

AC:

149

ALSPAC

AF:

0.0301

AC:

116

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.0303

AC:

256

ExAC

AF:

0.0480

AC:

5795

Asia WGS

AF:

0.102

AC:

354

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

MDN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

T;.

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.12

Sift

Benign

0.066

T;.

Polyphen

0.61

P;P

Vest4

0.49

MPC

0.50

ClinPred

0.029

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over