10-72368083-C-A

Variant names:

• chr10-72368083-C-A
• rs74145761
• NM_001195518.2:c.*112G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195518.2(MICU1):​c.*112G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000974 in 1,026,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.*112G>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10	c.*112G>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 9.74e-7 AC: 1 AN: 1026880 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 508102

African (AFR) AF: 0.00 AC: 0 AN: 23232

American (AMR) AF: 0.0000389 AC: 1 AN: 25720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18294

East Asian (EAS) AF: 0.00 AC: 0 AN: 33394

South Asian (SAS) AF: 0.00 AC: 0 AN: 60176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 775300

Other (OTH) AF: 0.00 AC: 0 AN: 44650

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		0.35
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

Other links and lift over

dbSNP: rs74145761; hg19: chr10-74127841;