NM_001195518.2:c.652+6596G>A

Variant names:

• chr10-72501559-C-T
• rs12356915
• NM_001195518.2:c.652+6596G>A

Variant summary

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

The NM_001195518.2(MICU1):​c.652+6596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,396 control chromosomes in the GnomAD database, including 7,604 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 0.28 (7604 hom., cov: 31)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• 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):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• proximal myopathy with extrapyramidal signs

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

ENSG00000226163 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 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.652+6596G>A		intron	N/A	NP_001182447.1	Q9BPX6-1
	MICU1	NM_001441218.1		c.883+6596G>A		intron	N/A	NP_001428147.1
	MICU1	NM_001441219.1		c.820+6596G>A		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.652+6596G>A		intron	N/A	ENSP00000354415.5	Q9BPX6-1
	MICU1	ENST00000964210.1		c.883+6596G>A		intron	N/A	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.820+6596G>A		intron	N/A	ENSP00000568036.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41894 AN: 151278 Hom.: 7607 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.277 AC: 41889 AN: 151396 Hom.: 7604 Cov.: 31 AF XY: 0.268 AC XY: 19846 AN XY: 73940

African (AFR) AF: 0.0735 AC: 3031 AN: 41242

American (AMR) AF: 0.290 AC: 4411 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3460

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1024 AN: 4792

European-Finnish (FIN) AF: 0.297 AC: 3083 AN: 10370

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28102 AN: 67856

Other (OTH) AF: 0.293 AC: 618 AN: 2108

Alfa AF: 0.352 Hom.: 16530

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.28
PhyloP100		-0.51
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: rs12356915; hg19: chr10-74261317;