chr10-72423159-T-C

Position:

• chr10-72423159-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195518.2(MICU1):​c.1071+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,528,368 control chromosomes in the GnomAD database, including 309,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23160 hom., cov: 30)
  • Exomes 𝑓: 0.63 (285892 hom.)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.431

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-72423159-T-C is Benign according to our data. Variant chr10-72423159-T-C is described in ClinVar as [Benign]. Clinvar id is 1277387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.1071+75A>G		intron_variant		ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10	c.1071+75A>G		intron_variant		1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80599 AN: 151834 Hom.: 23165 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.628

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.632 AC: 869266 AN: 1376416 Hom.: 285892 AF XY: 0.630 AC XY: 427327 AN XY: 678502

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.0614

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.531 AC: 80612 AN: 151952 Hom.: 23160 Cov.: 30 AF XY: 0.517 AC XY: 38387 AN XY: 74306

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.541

Alfa AF: 0.597 Hom.: 3520

Bravo AF: 0.520

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.55

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: rs10823922; hg19: chr10-74182917;