NM_001195518.2:c.*90G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001195518.2(MICU1):​c.*90G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,384,102 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (41 hom., cov: 31)
  • Exomes 𝑓: 0.025 (438 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.323
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-72368105-C-G is Benign according to our data. Variant chr10-72368105-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1205683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0191 (2907/152154) while in subpopulation SAS AF = 0.0408 (197/4830). AF 95% confidence interval is 0.0361. There are 41 homozygotes in GnomAd4. There are 1441 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

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>C		3_prime_UTR	Exon 12 of 12	NP_001182447.1	Q9BPX6-1
	MICU1	NM_001441218.1		c.*90G>C		3_prime_UTR	Exon 13 of 13	NP_001428147.1
	MICU1	NM_001441219.1		c.*90G>C		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>C		3_prime_UTR	Exon 12 of 12	ENSP00000354415.5	Q9BPX6-1
	MICU1	ENST00000964210.1		c.*90G>C		3_prime_UTR	Exon 13 of 13	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.*90G>C		3_prime_UTR	Exon 13 of 13	ENSP00000568036.1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2905 AN: 152036 Hom.: 41 Cov.: 31

Gnomad AFR AF: 0.00655

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0245 AC: 30207 AN: 1231948 Hom.: 438 Cov.: 17 AF XY: 0.0248 AC XY: 14967 AN XY: 604382

African (AFR) AF: 0.00738 AC: 206 AN: 27910

American (AMR) AF: 0.0281 AC: 807 AN: 28692

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 449 AN: 20898

East Asian (EAS) AF: 0.0336 AC: 1178 AN: 35098

South Asian (SAS) AF: 0.0385 AC: 2634 AN: 68438

European-Finnish (FIN) AF: 0.0133 AC: 623 AN: 46942

Middle Eastern (MID) AF: 0.0249 AC: 89 AN: 3578

European-Non Finnish (NFE) AF: 0.0242 AC: 22982 AN: 948906

Other (OTH) AF: 0.0241 AC: 1239 AN: 51486

GnomAD4 genome AF: 0.0191 AC: 2907 AN: 152154 Hom.: 41 Cov.: 31 AF XY: 0.0194 AC XY: 1441 AN XY: 74378

African (AFR) AF: 0.00660 AC: 274 AN: 41514

American (AMR) AF: 0.0192 AC: 293 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3470

East Asian (EAS) AF: 0.0345 AC: 178 AN: 5166

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4830

European-Finnish (FIN) AF: 0.0144 AC: 152 AN: 10580

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1653 AN: 67984

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0206 Hom.: 8

Bravo AF: 0.0194

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV63148877; COSMIC: COSV63148877;