rs4707557

Positions:

• chr6-89653064-A-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MDN1	NM_014611.3	c.15753T>G	p.Asn5251Lys	missense_variant	94/102	ENST00000369393.8
MDN1-AS1	NR_111915.1	n.105+14428A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDN1	ENST00000369393.8	c.15753T>G	p.Asn5251Lys	missense_variant	94/102	1	NM_014611.3	P1

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

GnomAD3 exomes AF: 0.114 AC: 28783 AN: 251422 Hom.: 4176 AF XY: 0.0976 AC XY: 13268 AN XY: 135886

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 SAS exome AF: 0.0261

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

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.0864

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.0256

Gnomad4 FIN exome AF: 0.0801

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0679

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

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0903

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0447 Hom.: 827

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 v4.3

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;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;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
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	T
GERP RS		1.3
Varity_R		0.045
gMVP		0.061

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: rs4707557; hg19: chr6-90362783; COSMIC: COSV65521058;