dbSNP rs4707557: MDN1:p.Asn5251Lys (chr6-89653064-A-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_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. 15/21 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 0.12 ( 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

Publications

15 publications found

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:40837): (MDN1 antisense RNA 1)

MDN1-AS1 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=7.253885E-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 rank	MANE	Protein	UniProt
MDN1	NM_014611.3 link	c.15753T>G	p.Asn5251Lys	missense_variant	Exon 94 of 102	ENST00000369393.8	NP_055426.1	Q9NU22
MDN1-AS1	NR_111915.1 link	n.105+14428A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8 link	c.15753T>G	p.Asn5251Lys	missense_variant	Exon 94 of 102	1	NM_014611.3	ENSP00000358400.3		Q9NU22

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

GnomAD2 exomes

AF:

0.114

AC:

28783

AN:

251422

AF XY:

0.0976

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 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

African (AFR)

AF:

0.256

AC:

8573

AN:

33470

American (AMR)

AF:

0.288

AC:

12862

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0864

AC:

2256

AN:

26126

East Asian (EAS)

AF:

0.481

AC:

19092

AN:

39676

South Asian (SAS)

AF:

0.0256

AC:

2207

AN:

86252

European-Finnish (FIN)

AF:

0.0801

AC:

4279

AN:

53418

Middle Eastern (MID)

AF:

0.0602

AC:

347

AN:

5764

European-Non Finnish (NFE)

AF:

0.0157

AC:

17472

AN:

1111736

Other (OTH)

AF:

0.0679

AC:

4098

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

3128

6255

9383

12510

15638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1124

2248

3372

4496

5620

<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:

0.125

AC:

18965

AN:

151886

Hom.:

2299

Cov.:

AF XY:

0.127

AC XY:

9443

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.248

AC:

10251

AN:

41384

American (AMR)

AF:

0.216

AC:

3301

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0903

AC:

313

AN:

3468

East Asian (EAS)

AF:

0.445

AC:

2300

AN:

5164

South Asian (SAS)

AF:

0.0356

AC:

171

AN:

4810

European-Finnish (FIN)

AF:

0.0874

AC:

922

AN:

10550

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0210

AC:

1427

AN:

67940

Other (OTH)

AF:

0.122

AC:

257

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

742

1484

2225

2967

3709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0574

Hom.:

2844

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

(source)

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

PhyloP100

0.096

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

Mutation Taster

=95/5

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