Variant 10-72368386-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001195518.2(MICU1):c.1271-31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,601,568 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 30 hom. )

Consequence

MICU1
NM_001195518.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.53

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 -16 ACMG points.

BP6

Variant 10-72368386-A-C is Benign according to our data. Variant chr10-72368386-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1210618.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 = 0.00106 (162/152342) while in subpopulation SAS AF= 0.0135 (65/4828). AF 95% confidence interval is 0.0108. There are 3 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU1	NM_001195518.2 linkuse as main transcript	c.1271-31T>G		intron_variant		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.1271-31T>G		intron_variant		1	NM_001195518.2	ENSP00000354415	P4	Q9BPX6-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00276

AC:

680

AN:

246414

Hom.:

AF XY:

0.00321

AC XY:

430

AN XY:

133870

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.00629

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.000917

Gnomad OTH exome

AF:

0.00349

GnomAD4 exome

AF:

0.00157

AC:

2277

AN:

1449226

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1426

AN XY:

718300

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000628

Gnomad4 ASJ exome

AF:

0.00580

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.000534

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152342

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.000782

Asia WGS

AF:

0.00462

AC:

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	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.59

BranchPoint Hunter

7.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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