10-72368105-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.323

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1205683.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.*90G>C		3_prime_UTR_variant	12/12	ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.*90G>C		3_prime_UTR_variant	12/12	1	NM_001195518.2	P4

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

Gnomad4 AFR exome AF: 0.00738

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0215

Gnomad4 EAS exome AF: 0.0336

Gnomad4 SAS exome AF: 0.0385

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.0241

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

Gnomad4 AFR AF: 0.00660

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0206 Hom.: 8

Bravo AF: 0.0194

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.47
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

Publications

LitVar

Other links and lift over

dbSNP: rs41282272; hg19: chr10-74127863; COSMIC: COSV63148877; COSMIC: COSV63148877;