dbSNP rs41273327: MDN1:p.Arg4266Gly (chr6-89674555-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict 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

Publications

12 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

new If you want to explore the variant's impact on the transcript NM_014611.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014611.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDN1	NM_014611.3	MANE Select	c.12796A>G	p.Arg4266Gly	missense	Exon 79 of 102	NP_055426.1	Q9NU22
	MDN1-AS1	NR_111915.1		n.106-841T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDN1	ENST00000369393.8	TSL:1 MANE Select	c.12796A>G	p.Arg4266Gly	missense	Exon 79 of 102	ENSP00000358400.3	Q9NU22
MDN1	ENST00000700643.1		n.3496A>G		non_coding_transcript_exon	Exon 20 of 41
MDN1	ENST00000700647.1		n.3496A>G		non_coding_transcript_exon	Exon 20 of 44

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

GnomAD2 exomes

AF:

0.0508

AC:

11536

AN:

227120

AF XY:

0.0540

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 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

African (AFR)

AF:

0.0253

AC:

840

AN:

33174

American (AMR)

AF:

0.0585

AC:

2550

AN:

43576

Ashkenazi Jewish (ASJ)

AF:

0.0321

AC:

810

AN:

25248

East Asian (EAS)

AF:

0.0291

AC:

1150

AN:

39526

South Asian (SAS)

AF:

0.124

AC:

10530

AN:

84852

European-Finnish (FIN)

AF:

0.0291

AC:

1222

AN:

41994

Middle Eastern (MID)

AF:

0.0654

AC:

320

AN:

4896

European-Non Finnish (NFE)

AF:

0.0332

AC:

36745

AN:

1105364

Other (OTH)

AF:

0.0457

AC:

2726

AN:

59622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

3060

6121

9181

12242

15302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1468

2936

4404

5872

7340

<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:

0.0345

AC:

5252

AN:

152330

Hom.:

124

Cov.:

AF XY:

0.0368

AC XY:

2739

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0215

AC:

893

AN:

41588

American (AMR)

AF:

0.0489

AC:

748

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3472

East Asian (EAS)

AF:

0.0392

AC:

203

AN:

5174

South Asian (SAS)

AF:

0.130

AC:

626

AN:

4830

European-Finnish (FIN)

AF:

0.0229

AC:

243

AN:

10628

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0332

AC:

2259

AN:

68022

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

262

524

785

1047

1309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0341

Hom.:

322

Bravo

AF:

0.0351

Asia WGS

AF:

0.102

AC:

354

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MDN1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.041

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.6

PhyloP100

1.1

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.12

Sift

Benign

0.066

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.28

Mutation Taster

=91/9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over