chr10-72552514-A-G

Variant names:

• chr10-72552514-A-G
• rs11000348
• NM_001195518.2:c.331-1173T>C

Variant summary

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

The NM_001195518.2(MICU1):​c.331-1173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,026 control chromosomes in the GnomAD database, including 27,893 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 0.59 (27893 hom., cov: 32)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484
• Publications: 3 publications found

Genes affected

MICU1 (HGNC:1530): (mitochondrial calcium uptake 1) This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2013]

MICU1 Gene-Disease associations (from GenCC):

• proximal myopathy with extrapyramidal signs

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195518.2. 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
	MICU1	NM_001195518.2	MANE Select	c.331-1173T>C		intron	N/A	NP_001182447.1
	MICU1	NM_001441218.1		c.331-1173T>C		intron	N/A	NP_001428147.1
	MICU1	NM_001441219.1		c.331-1173T>C		intron	N/A	NP_001428148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	ENST00000361114.10	TSL:1 MANE Select	c.331-1173T>C		intron	N/A	ENSP00000354415.5
	MICU1	ENST00000964210.1		c.331-1173T>C		intron	N/A	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.331-1173T>C		intron	N/A	ENSP00000568036.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89919 AN: 151908 Hom.: 27886 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.599

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 89962 AN: 152026 Hom.: 27893 Cov.: 32 AF XY: 0.574 AC XY: 42675 AN XY: 74288

African (AFR) AF: 0.593 AC: 24583 AN: 41452

American (AMR) AF: 0.511 AC: 7809 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1951 AN: 3470

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5186

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.495 AC: 5214 AN: 10536

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46043 AN: 67970

Other (OTH) AF: 0.595 AC: 1257 AN: 2114

Alfa AF: 0.653 Hom.: 23882

Bravo AF: 0.590

Asia WGS AF: 0.257 AC: 895 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		0.48
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: rs11000348; hg19: chr10-74312272;