Variant 6-89645070-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_014611.3(MDN1):c.16547C>T(p.Ala5516Val) variant causes a missense change. The variant allele was found at a frequency of 0.00296 in 1,610,774 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

MDN1
NM_014611.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.42

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-AS1 (HGNC:):

MDN1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, MDN1

BP4

Computational evidence support a benign effect (MetaRNN=0.00670591).

BP6

Variant 6-89645070-G-A is Benign according to our data. Variant chr6-89645070-G-A is described in ClinVar as [Benign]. Clinvar id is 440952.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDN1	NM_014611.3 linkuse as main transcript	c.16547C>T	p.Ala5516Val	missense_variant	101/102	ENST00000369393.8
MDN1-AS1	NR_111915.1 linkuse as main transcript	n.105+6434G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDN1	ENST00000369393.8 linkuse as main transcript	c.16547C>T	p.Ala5516Val	missense_variant	101/102	1	NM_014611.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

367

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00351

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00304

AC:

765

AN:

251372

Hom.:

AF XY:

0.00282

AC XY:

383

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00868

Gnomad NFE exome

AF:

0.00462

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00302

AC:

4404

AN:

1458468

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2111

AN XY:

725054

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00937

Gnomad4 NFE exome

AF:

0.00334

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152306

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

200

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.00351

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00322

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00348

AC:

423

EpiCase

AF:

0.00285

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MDN1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 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). -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

T;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;.

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.083

Sift

Benign

0.071

T;.

Polyphen

0.058

B;B

Vest4

0.71

MVP

0.30

MPC

0.15

ClinPred

0.022

GERP RS

5.2

Varity_R

0.15

gMVP

0.68

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