chr10-72381281-T-C

Variant names:

• chr10-72381281-T-C
• rs7903091
• NM_001195518.2:c.1181-5409A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195518.2(MICU1):​c.1181-5409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,982 control chromosomes in the GnomAD database, including 24,358 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 0.56 (24358 hom., cov: 31)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• proximal myopathy with extrapyramidal signs

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.1181-5409A>G		intron_variant	Intron 10 of 11	ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10	c.1181-5409A>G		intron_variant	Intron 10 of 11	1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84308 AN: 151864 Hom.: 24348 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.555 AC: 84358 AN: 151982 Hom.: 24358 Cov.: 31 AF XY: 0.542 AC XY: 40241 AN XY: 74272

African (AFR) AF: 0.503 AC: 20835 AN: 41440

American (AMR) AF: 0.492 AC: 7514 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3470

East Asian (EAS) AF: 0.153 AC: 788 AN: 5166

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4822

European-Finnish (FIN) AF: 0.488 AC: 5149 AN: 10542

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43979 AN: 67968

Other (OTH) AF: 0.562 AC: 1184 AN: 2108

Alfa AF: 0.573 Hom.: 9102

Bravo AF: 0.553

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.26
DANN	Benign	0.60
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7903091; hg19: chr10-74141039;