NM_001195518.2:c.*112G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195518.2(MICU1):​c.*112G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,178,878 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (115 hom., cov: 30)
  • Exomes 𝑓: 0.0079 (191 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-72368083-C-T is Benign according to our data. Variant chr10-72368083-C-T is described in ClinVar as [Benign]. Clinvar id is 1245940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3407 AN: 151942 Hom.: 111 Cov.: 30

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0221

GnomAD4 exome AF: 0.00785 AC: 8064 AN: 1026818 Hom.: 191 Cov.: 13 AF XY: 0.00817 AC XY: 4150 AN XY: 508076

African (AFR) AF: 0.0562 AC: 1305 AN: 23224

American (AMR) AF: 0.00809 AC: 208 AN: 25718

Ashkenazi Jewish (ASJ) AF: 0.00224 AC: 41 AN: 18294

East Asian (EAS) AF: 0.0850 AC: 2836 AN: 33380

South Asian (SAS) AF: 0.0225 AC: 1356 AN: 60162

European-Finnish (FIN) AF: 0.00519 AC: 223 AN: 42976

Middle Eastern (MID) AF: 0.00574 AC: 18 AN: 3136

European-Non Finnish (NFE) AF: 0.00196 AC: 1522 AN: 775286

Other (OTH) AF: 0.0124 AC: 555 AN: 44642

GnomAD4 genome AF: 0.0225 AC: 3424 AN: 152060 Hom.: 115 Cov.: 30 AF XY: 0.0222 AC XY: 1651 AN XY: 74324

African (AFR) AF: 0.0588 AC: 2439 AN: 41452

American (AMR) AF: 0.0107 AC: 164 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.0843 AC: 435 AN: 5160

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4808

European-Finnish (FIN) AF: 0.00681 AC: 72 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 68000

Other (OTH) AF: 0.0218 AC: 46 AN: 2106

Alfa AF: 0.00329 Hom.: 0

Bravo AF: 0.0250

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.80
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs74145761; hg19: chr10-74127841;