chr6-89653064-A-C

Variant names:

• chr6-89653064-A-C
• rs4707557
• NM_014611.3:c.15753T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 15 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 -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.

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.15753T>G	p.Asn5251Lys	missense	Exon 94 of 102	NP_055426.1	Q9NU22
	MDN1-AS1	NR_111915.1		n.105+14428A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDN1	ENST00000369393.8	TSL:1 MANE Select	c.15753T>G	p.Asn5251Lys	missense	Exon 94 of 102	ENSP00000358400.3	Q9NU22
	MDN1	ENST00000700640.1		n.2316T>G		non_coding_transcript_exon	Exon 9 of 17
	MDN1	ENST00000700641.1		n.3872T>G		non_coding_transcript_exon	Exon 8 of 16

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18938 AN: 151768 Hom.: 2292 Cov.: 33

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

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.: 31 AF XY: 0.0463 AC XY: 33637 AN XY: 727084

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

GnomAD4 genome AF: 0.125 AC: 18965 AN: 151886 Hom.: 2299 Cov.: 33 AF XY: 0.127 AC XY: 9443 AN XY: 74240

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: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1427 AN: 67940

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.0574 Hom.: 2844

Bravo AF: 0.144

TwinsUK AF: 0.0205 AC: 76

ALSPAC AF: 0.0169 AC: 65

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.89
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.00073	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.096
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.033
Sift	Benign	0.82	T
Polyphen		0.089	B
Vest4		0.065
MutPred		0.12		Gain of ubiquitination at N5251 (P = 0.0128)
MPC		0.17
ClinPred		0.0032	T
GERP RS		1.3
Varity_R		0.045
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: rs4707557; hg19: chr6-90362783; COSMIC: COSV65521058;