rs10823935

Variant names:

• chr10-72566289-A-G
• rs10823935
• NM_001195518.2:c.161+344T>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.161+344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,866 control chromosomes in the GnomAD database, including 31,611 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 0.63 (31611 hom., cov: 30)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 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.161+344T>C		intron	N/A	NP_001182447.1	Q9BPX6-1
	MICU1	NM_001441218.1		c.161+344T>C		intron	N/A	NP_001428147.1
	MICU1	NM_001441219.1		c.161+344T>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.161+344T>C		intron	N/A	ENSP00000354415.5	Q9BPX6-1
	MICU1	ENST00000964210.1		c.161+344T>C		intron	N/A	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.161+344T>C		intron	N/A	ENSP00000568036.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95504 AN: 151748 Hom.: 31586 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.629 AC: 95571 AN: 151866 Hom.: 31611 Cov.: 30 AF XY: 0.611 AC XY: 45333 AN XY: 74202

African (AFR) AF: 0.722 AC: 29922 AN: 41418

American (AMR) AF: 0.528 AC: 8053 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.0420 AC: 217 AN: 5164

South Asian (SAS) AF: 0.440 AC: 2118 AN: 4812

European-Finnish (FIN) AF: 0.493 AC: 5188 AN: 10516

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46063 AN: 67932

Other (OTH) AF: 0.617 AC: 1296 AN: 2102

Alfa AF: 0.662 Hom.: 4382

Bravo AF: 0.633

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.33
PhyloP100		-0.54
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: rs10823935; hg19: chr10-74326047;