rs796052156

Variant names:

• chr6-89695654-A-G
• rs796052156
• NM_014611.3:c.9722T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP3_Moderate BP6

The NM_014611.3(MDN1):​c.9722T>C​(p.Phe3241Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MDN1 NM_014611.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 8.95
• Publications: 1 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906
• BP6: Variant 6-89695654-A-G is Benign according to our data. Variant chr6-89695654-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 207856.Status of the report is no_assertion_criteria_provided, 0 stars.

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.9722T>C	p.Phe3241Ser	missense	Exon 61 of 102	NP_055426.1	Q9NU22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDN1	ENST00000369393.8	TSL:1 MANE Select	c.9722T>C	p.Phe3241Ser	missense	Exon 61 of 102	ENSP00000358400.3	Q9NU22
	MDN1	ENST00000700643.1		n.422T>C		non_coding_transcript_exon	Exon 2 of 41
	MDN1	ENST00000700647.1		n.422T>C		non_coding_transcript_exon	Exon 2 of 44

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460276 Hom.: 0 Cov.: 36 AF XY: 0.00000689 AC XY: 5 AN XY: 726200

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111222

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		8.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.66		Gain of relative solvent accessibility (P = 0.005)
MVP		0.48
MPC		0.87
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.60
gMVP		0.66
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs796052156; hg19: chr6-90405373;