NM_014611.3:c.14159T>C

Variant names:

• chr6-89664564-A-G
• rs16882046
• NM_014611.3:c.14159T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014611.3(MDN1):​c.14159T>C​(p.Ile4720Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,613,510 control chromosomes in the GnomAD database, including 1,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (126 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1708 hom.)
• Consequence: MDN1 NM_014611.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 7.36
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016413033).
• BP6: Variant 6-89664564-A-G is Benign according to our data. Variant chr6-89664564-A-G is described in ClinVar as Benign. ClinVar VariationId is 403077.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.14159T>C	p.Ile4720Thr	missense	Exon 85 of 102	NP_055426.1	Q9NU22
	MDN1-AS1	NR_111915.1		n.106-10832A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDN1	ENST00000369393.8	TSL:1 MANE Select	c.14159T>C	p.Ile4720Thr	missense	Exon 85 of 102	ENSP00000358400.3	Q9NU22
	MDN1	ENST00000700641.1		n.207T>C		non_coding_transcript_exon	Exon 1 of 16
	MDN1	ENST00000700642.1		n.999T>C		non_coding_transcript_exon	Exon 1 of 18

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5222 AN: 152170 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0372

GnomAD2 exomes AF: 0.0490 AC: 12320 AN: 251180 AF XY: 0.0525

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.0598

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.0404

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0350

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0394 AC: 57561 AN: 1461222 Hom.: 1708 Cov.: 30 AF XY: 0.0420 AC XY: 30499 AN XY: 726944

African (AFR) AF: 0.0251 AC: 839 AN: 33460

American (AMR) AF: 0.0580 AC: 2589 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0321 AC: 838 AN: 26128

East Asian (EAS) AF: 0.0290 AC: 1150 AN: 39662

South Asian (SAS) AF: 0.124 AC: 10679 AN: 86140

European-Finnish (FIN) AF: 0.0291 AC: 1552 AN: 53416

Middle Eastern (MID) AF: 0.0735 AC: 424 AN: 5768

European-Non Finnish (NFE) AF: 0.0331 AC: 36740 AN: 1111608

Other (OTH) AF: 0.0456 AC: 2750 AN: 60364

GnomAD4 genome AF: 0.0343 AC: 5226 AN: 152288 Hom.: 126 Cov.: 32 AF XY: 0.0365 AC XY: 2720 AN XY: 74454

African (AFR) AF: 0.0211 AC: 879 AN: 41562

American (AMR) AF: 0.0489 AC: 749 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5178

South Asian (SAS) AF: 0.129 AC: 625 AN: 4828

European-Finnish (FIN) AF: 0.0229 AC: 243 AN: 10608

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2248 AN: 68018

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0346 Hom.: 445

Bravo AF: 0.0349

TwinsUK AF: 0.0399 AC: 148

ALSPAC AF: 0.0306 AC: 118

ESP6500AA AF: 0.0222 AC: 98

ESP6500EA AF: 0.0347 AC: 298

ExAC AF: 0.0487 AC: 5915

Asia WGS AF: 0.102 AC: 354 AN: 3478

EpiCase AF: 0.0384

EpiControl AF: 0.0401

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MDN1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.34	T
Polyphen		0.015	B
Vest4		0.11
MPC		0.25
ClinPred		0.032	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.032
gMVP		0.061
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16882046; hg19: chr6-90374283; COSMIC: COSV107468157;