Genetic Variant MICU1:c.933+41A>G (chr10-72475059-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195518.2(MICU1):c.933+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,550,644 control chromosomes in the GnomAD database, including 345,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35417 hom., cov: 32)

Exomes 𝑓: 0.66 ( 309627 hom. )

Consequence

MICU1
NM_001195518.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.440

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-72475059-T-C is Benign according to our data. Variant chr10-72475059-T-C is described in ClinVar as [Benign]. Clinvar id is 1225614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU1	NM_001195518.2 link	c.933+41A>G		intron_variant	Intron 8 of 11	ENST00000361114.10	NP_001182447.1	Q9BPX6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10 link	c.933+41A>G		intron_variant	Intron 8 of 11	1	NM_001195518.2	ENSP00000354415.5		Q9BPX6-1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101724

AN:

151970

Hom.:

35382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.654

GnomAD3 exomes

AF:

0.588

AC:

111844

AN:

190168

Hom.:

34817

AF XY:

0.592

AC XY:

59624

AN XY:

100754

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.444

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.534

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.658

AC:

920897

AN:

1398556

Hom.:

309627

Cov.:

AF XY:

0.656

AC XY:

454024

AN XY:

692024

show subpopulations

Gnomad4 AFR exome

AF:

0.826

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.267

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.692

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.669

AC:

101803

AN:

152088

Hom.:

35417

Cov.:

AF XY:

0.653

AC XY:

48526

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.821

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.514

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.679

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.618

Hom.:

4216

Bravo

AF:

0.679

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.7

DANN

Benign

0.30

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