Variant rs4707557 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014611.3(MDN1):c.15753T>G(p.Asn5251Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,613,422 control chromosomes in the GnomAD database, including 10,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 2299 hom., cov: 33)

Exomes 𝑓: 0.049 ( 8521 hom. )

Consequence

MDN1
NM_014611.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.253885E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 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.15753T>G	p.Asn5251Lys	missense_variant	94/102	ENST00000369393.8	NP_055426.1
MDN1-AS1	NR_111915.1 linkuse as main transcript	n.105+14428A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8 linkuse as main transcript	c.15753T>G	p.Asn5251Lys	missense_variant	94/102	1	NM_014611.3	ENSP00000358400	P1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18938

AN:

151768

Hom.:

2292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.0903

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.0355

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.114

AC:

28783

AN:

251422

Hom.:

4176

AF XY:

0.0976

AC XY:

13268

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.0859

Gnomad EAS exome

AF:

0.453

Gnomad SAS exome

AF:

0.0261

Gnomad FIN exome

AF:

0.0817

Gnomad NFE exome

AF:

0.0201

Gnomad OTH exome

AF:

0.0850

GnomAD4 exome

AF:

0.0487

AC:

71186

AN:

1461536

Hom.:

8521

Cov.:

AF XY:

0.0463

AC XY:

33637

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.0864

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.0256

Gnomad4 FIN exome

AF:

0.0801

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0679

GnomAD4 genome

AF:

0.125

AC:

18965

AN:

151886

Hom.:

2299

Cov.:

AF XY:

0.127

AC XY:

9443

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.0903

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.0356

Gnomad4 FIN

AF:

0.0874

Gnomad4 NFE

AF:

0.0210

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.0447

Hom.:

827

Bravo

AF:

0.144

TwinsUK

AF:

0.0205

AC:

ALSPAC

AF:

0.0169

AC:

ESP6500AA

AF:

0.241

AC:

1060

ESP6500EA

AF:

0.0194

AC:

167

ExAC

AF:

0.105

AC:

12734

Asia WGS

AF:

0.199

AC:

690

AN:

3476

EpiCase

AF:

0.0202

EpiControl

AF:

0.0194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.6

DANN

Benign

0.89

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.50

T;.

MetaRNN

Benign

0.00073

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.033

Sift

Benign

0.82

T;.

Polyphen

0.089

B;B

Vest4

0.065

MutPred

0.12

Gain of ubiquitination at N5251 (P = 0.0128);Gain of ubiquitination at N5251 (P = 0.0128);

MPC

0.17

ClinPred

0.0032

GERP RS

1.3

Varity_R

0.045

gMVP

0.061

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over