rs4262652

Variant names:

• chr10-72368095-G-A
• rs4262652
• NM_001195518.2:c.*100C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-72368095-G-A
• chr10-72368095-G-C

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.*100C>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 0.603 in 1,261,036 control chromosomes in the GnomAD database, including 236,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22841 hom., cov: 30)
  • Exomes 𝑓: 0.61 (213462 hom.)
• Consequence: MICU1 NM_001195518.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.641
• Publications: 17 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=-0.89).
• BP6: Variant 10-72368095-G-A is Benign according to our data. Variant chr10-72368095-G-A is described in ClinVar as [Benign]. Clinvar id is 1291021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.*100C>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.*100C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81596 AN: 151772 Hom.: 22825 Cov.: 30

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.612 AC: 678795 AN: 1109146 Hom.: 213462 Cov.: 15 AF XY: 0.610 AC XY: 333581 AN XY: 546844

African (AFR) AF: 0.455 AC: 11454 AN: 25160

American (AMR) AF: 0.454 AC: 12373 AN: 27260

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 10157 AN: 19386

East Asian (EAS) AF: 0.191 AC: 6493 AN: 34082

South Asian (SAS) AF: 0.529 AC: 33622 AN: 63568

European-Finnish (FIN) AF: 0.496 AC: 22408 AN: 45180

Middle Eastern (MID) AF: 0.654 AC: 2179 AN: 3332

European-Non Finnish (NFE) AF: 0.655 AC: 552400 AN: 843834

Other (OTH) AF: 0.585 AC: 27709 AN: 47344

GnomAD4 genome AF: 0.538 AC: 81646 AN: 151890 Hom.: 22841 Cov.: 30 AF XY: 0.526 AC XY: 39006 AN XY: 74226

African (AFR) AF: 0.466 AC: 19273 AN: 41396

American (AMR) AF: 0.497 AC: 7580 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3470

East Asian (EAS) AF: 0.158 AC: 814 AN: 5164

South Asian (SAS) AF: 0.499 AC: 2403 AN: 4820

European-Finnish (FIN) AF: 0.467 AC: 4929 AN: 10550

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

European-Non Finnish (NFE) AF: 0.632 AC: 42943 AN: 67922

Other (OTH) AF: 0.559 AC: 1174 AN: 2102

Alfa AF: 0.598 Hom.: 76483

Bravo AF: 0.535

Asia WGS AF: 0.320 AC: 1115 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 23, 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	-0.89
CADD	Benign	0.86
DANN	Benign	0.49
PhyloP100		-0.64
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: rs4262652; hg19: chr10-74127853; COSMIC: COSV63144545; COSMIC: COSV63144545;