10-72368083-C-T

Position:

• chr10-72368083-C-T

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.*112G>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 0.00974 in 1,178,878 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (115 hom., cov: 30)
  • Exomes 𝑓: 0.0079 (191 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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=-0.8).
• BP6: Variant 10-72368083-C-T is Benign according to our data. Variant chr10-72368083-C-T is described in ClinVar as [Benign]. Clinvar id is 1245940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.*112G>A		3_prime_UTR_variant	12/12	ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.*112G>A		3_prime_UTR_variant	12/12	1	NM_001195518.2	P4

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3407 AN: 151942 Hom.: 111 Cov.: 30

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0221

GnomAD4 exome AF: 0.00785 AC: 8064 AN: 1026818 Hom.: 191 Cov.: 13 AF XY: 0.00817 AC XY: 4150 AN XY: 508076

Gnomad4 AFR exome AF: 0.0562

Gnomad4 AMR exome AF: 0.00809

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.0850

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.00519

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0225 AC: 3424 AN: 152060 Hom.: 115 Cov.: 30 AF XY: 0.0222 AC XY: 1651 AN XY: 74324

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.0239

Gnomad4 FIN AF: 0.00681

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.00329 Hom.: 0

Bravo AF: 0.0250

Asia WGS AF: 0.0630 AC: 219 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 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.80
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: rs74145761; hg19: chr10-74127841;