dbSNP rs10509343: MICU1:c.494-37T>A (chr10-72533826-A-T) – 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.494-37T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,409,988 control chromosomes in the GnomAD database, including 300,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31128 hom., cov: 32)

Exomes 𝑓: 0.64 ( 268972 hom. )

Consequence

MICU1
NM_001195518.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.196

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=-0.88).

BP6

Variant 10-72533826-A-T is Benign according to our data. Variant chr10-72533826-A-T is described in ClinVar as [Benign]. Clinvar id is 1248259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU1	NM_001195518.2 link	c.494-37T>A		intron_variant	Intron 4 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.494-37T>A		intron_variant	Intron 4 of 11	1	NM_001195518.2	ENSP00000354415.5		Q9BPX6-1

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94746

AN:

151496

Hom.:

31104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.620

GnomAD3 exomes

AF:

0.562

AC:

96089

AN:

171082

Hom.:

29692

AF XY:

0.565

AC XY:

51919

AN XY:

91956

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.0326

Gnomad SAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.683

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.641

AC:

806504

AN:

1258374

Hom.:

268972

Cov.:

AF XY:

0.637

AC XY:

401496

AN XY:

629956

show subpopulations

Gnomad4 AFR exome

AF:

0.720

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.0673

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.524

Gnomad4 NFE exome

AF:

0.688

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.625

AC:

94812

AN:

151614

Hom.:

31128

Cov.:

AF XY:

0.607

AC XY:

44981

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.719

Gnomad4 AMR

AF:

0.526

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.0426

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.672

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.644

Hom.:

5920

Bravo

AF:

0.630

Asia WGS

AF:

0.268

AC:

933

AN:

3470

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

-0.88

CADD

Benign

0.43

DANN

Benign

0.78

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