Variant 10-72368105-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.323

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU1	NM_001195518.2 linkuse as main transcript	c.*90G>C		3_prime_UTR_variant	12/12	ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10 linkuse as main transcript	c.*90G>C		3_prime_UTR_variant	12/12	1	NM_001195518.2	ENSP00000354415	P4	Q9BPX6-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2905

AN:

152036

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0248

AC XY:

14967

AN XY:

604382

show subpopulations

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.:

Cov.:

AF XY:

0.0194

AC XY:

1441

AN XY:

74378

show subpopulations

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.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over