rs764108

Variant names:

• chr6-89722902-A-G
• rs764108
• NM_014611.3:c.5967+53T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MDN1	NM_014611.3	c.5967+53T>C		intron_variant	Intron 40 of 101	ENST00000369393.8	NP_055426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDN1	ENST00000369393.8	c.5967+53T>C		intron_variant	Intron 40 of 101	1	NM_014611.3	ENSP00000358400.3

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

African (AFR) AF: 0.191 AC: 5713 AN: 29840

American (AMR) AF: 0.131 AC: 4531 AN: 34462

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 4720 AN: 22122

East Asian (EAS) AF: 0.196 AC: 7584 AN: 38662

South Asian (SAS) AF: 0.106 AC: 7908 AN: 74622

European-Finnish (FIN) AF: 0.170 AC: 8683 AN: 51190

Middle Eastern (MID) AF: 0.137 AC: 727 AN: 5322

European-Non Finnish (NFE) AF: 0.180 AC: 187263 AN: 1041292

Other (OTH) AF: 0.181 AC: 10163 AN: 55996

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

African (AFR) AF: 0.190 AC: 7859 AN: 41468

American (AMR) AF: 0.167 AC: 2553 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1137 AN: 5162

South Asian (SAS) AF: 0.110 AC: 531 AN: 4808

European-Finnish (FIN) AF: 0.179 AC: 1877 AN: 10498

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12056 AN: 67962

Other (OTH) AF: 0.185 AC: 389 AN: 2106

Alfa AF: 0.176 Hom.: 1592

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
PhyloP100		1.2
Mutation Taster		=100/0	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: rs764108; hg19: chr6-90432621;