10-72368105-C-T

Variant names:

• chr10-72368105-C-T
• rs41282272
• NM_001195518.2:c.*90G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195518.2(MICU1):​c.*90G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000812 in 1,232,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.*90G>A		3_prime_UTR	Exon 12 of 12	NP_001182447.1	Q9BPX6-1
	MICU1	NM_001441218.1		c.*90G>A		3_prime_UTR	Exon 13 of 13	NP_001428147.1
	MICU1	NM_001441219.1		c.*90G>A		3_prime_UTR	Exon 13 of 13	NP_001428148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	ENST00000361114.10	TSL:1 MANE Select	c.*90G>A		3_prime_UTR	Exon 12 of 12	ENSP00000354415.5	Q9BPX6-1
	MICU1	ENST00000964210.1		c.*90G>A		3_prime_UTR	Exon 13 of 13	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.*90G>A		3_prime_UTR	Exon 13 of 13	ENSP00000568036.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.12e-7 AC: 1 AN: 1232192 Hom.: 0 Cov.: 17 AF XY: 0.00000165 AC XY: 1 AN XY: 604504

African (AFR) AF: 0.00 AC: 0 AN: 27910

American (AMR) AF: 0.00 AC: 0 AN: 28700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20902

East Asian (EAS) AF: 0.00 AC: 0 AN: 35100

South Asian (SAS) AF: 0.00 AC: 0 AN: 68450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949110

Other (OTH) AF: 0.0000194 AC: 1 AN: 51496

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs41282272; hg19: chr10-74127863;