rs764108

Positions:

• chr6-89722902-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014611.3(MDN1):​c.5967+53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,505,456 control chromosomes in the GnomAD database, including 23,949 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2499 hom., cov: 33)
  • Exomes 𝑓: 0.18 (21450 hom.)
• Consequence: MDN1 NM_014611.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDN1	NM_014611.3	c.5967+53T>C		intron_variant		ENST00000369393.8	NP_055426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8	c.5967+53T>C		intron_variant		1	NM_014611.3	ENSP00000358400	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27219 AN: 151844 Hom.: 2494 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.175 AC: 237292 AN: 1353508 Hom.: 21450 AF XY: 0.174 AC XY: 116822 AN XY: 670892

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.179 AC: 27242 AN: 151948 Hom.: 2499 Cov.: 33 AF XY: 0.180 AC XY: 13356 AN XY: 74262

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.185

Alfa AF: 0.175 Hom.: 1047

Bravo AF: 0.180

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.64

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: rs764108; hg19: chr6-90432621;