rs12356915

Positions:

• chr10-72501559-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195518.2(MICU1):​c.652+6596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,396 control chromosomes in the GnomAD database, including 7,604 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7604 hom., cov: 31)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.652+6596G>A		intron_variant		ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10	c.652+6596G>A		intron_variant		1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41894 AN: 151278 Hom.: 7607 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 41889 AN: 151396 Hom.: 7604 Cov.: 31 AF XY: 0.268 AC XY: 19846 AN XY: 73940

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.293

Alfa AF: 0.339 Hom.: 2273

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.28

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: rs12356915; hg19: chr10-74261317;