rs41273327

Variant names:

• chr6-89674555-T-C
• rs41273327
• NM_014611.3:c.12796A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.09

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-AS1 (HGNC:40837): (MDN1 antisense RNA 1)

ACMG classification

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 rank	MANE	Protein	UniProt
MDN1	NM_014611.3	c.12796A>G	p.Arg4266Gly	missense_variant	Exon 79 of 102	ENST00000369393.8	NP_055426.1
MDN1-AS1	NR_111915.1	n.106-841T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8	c.12796A>G	p.Arg4266Gly	missense_variant	Exon 79 of 102	1	NM_014611.3	ENSP00000358400.3

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5248 AN: 152212 Hom.: 127 Cov.: 32

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

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.: 32 AF XY: 0.0421 AC XY: 30098 AN XY: 714606

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.: 32 AF XY: 0.0368 AC XY: 2739 AN XY: 74486

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: 90

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

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T;.
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.37	T
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	T
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

Other links and lift over

dbSNP: rs41273327; hg19: chr6-90384274;