10-72368095-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195518.2(MICU1):c.*100C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,261,036 control chromosomes in the GnomAD database, including 236,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22841 hom., cov: 30)
  • Exomes 𝑓: 0.61 (213462 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.641

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=-0.89).
• BP6: Variant 10-72368095-G-A is Benign according to our data. Variant chr10-72368095-G-A is described in ClinVar as [Benign]. Clinvar id is 1291021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.*100C>T		3_prime_UTR_variant	12/12	ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.*100C>T		3_prime_UTR_variant	12/12	1	NM_001195518.2	P4

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81596 AN: 151772 Hom.: 22825 Cov.: 30

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.612 AC: 678795 AN: 1109146 Hom.: 213462 Cov.: 15 AF XY: 0.610 AC XY: 333581 AN XY: 546844

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.538 AC: 81646 AN: 151890 Hom.: 22841 Cov.: 30 AF XY: 0.526 AC XY: 39006 AN XY: 74226

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.559

Alfa AF: 0.609 Hom.: 47430

Bravo AF: 0.535

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.86
Dann	Benign	0.49
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: rs4262652; hg19: chr10-74127853; COSMIC: COSV63144545; COSMIC: COSV63144545;