10-72423159-T-C

Variant names:

• chr10-72423159-T-C
• rs10823922
• NM_001195518.2:c.1071+75A>G

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.1071+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,528,368 control chromosomes in the GnomAD database, including 309,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23160 hom., cov: 30)
  • Exomes 𝑓: 0.63 (285892 hom.)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.431
• Publications: 4 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 10-72423159-T-C is Benign according to our data. Variant chr10-72423159-T-C is described in ClinVar as Benign. ClinVar VariationId is 1277387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195518.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	NM_001195518.2	MANE Select	c.1071+75A>G		intron	N/A	NP_001182447.1
	MICU1	NM_001441218.1		c.1302+75A>G		intron	N/A	NP_001428147.1
	MICU1	NM_001441219.1		c.1239+75A>G		intron	N/A	NP_001428148.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	ENST00000361114.10	TSL:1 MANE Select	c.1071+75A>G		intron	N/A	ENSP00000354415.5
	MICU1	ENST00000642044.1		c.1089+75A>G		intron	N/A	ENSP00000493232.1
	MICU1	ENST00000635239.1	TSL:5	c.1083+75A>G		intron	N/A	ENSP00000489563.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80599 AN: 151834 Hom.: 23165 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.628

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.632 AC: 869266 AN: 1376416 Hom.: 285892 AF XY: 0.630 AC XY: 427327 AN XY: 678502

African (AFR) AF: 0.383 AC: 11873 AN: 30968

American (AMR) AF: 0.430 AC: 14885 AN: 34620

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 12052 AN: 21642

East Asian (EAS) AF: 0.0614 AC: 2382 AN: 38790

South Asian (SAS) AF: 0.488 AC: 36084 AN: 73944

European-Finnish (FIN) AF: 0.522 AC: 26286 AN: 50396

Middle Eastern (MID) AF: 0.646 AC: 3479 AN: 5386

European-Non Finnish (NFE) AF: 0.685 AC: 728761 AN: 1063926

Other (OTH) AF: 0.590 AC: 33464 AN: 56744

GnomAD4 genome AF: 0.531 AC: 80612 AN: 151952 Hom.: 23160 Cov.: 30 AF XY: 0.517 AC XY: 38387 AN XY: 74306

African (AFR) AF: 0.396 AC: 16387 AN: 41432

American (AMR) AF: 0.486 AC: 7417 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3468

East Asian (EAS) AF: 0.0367 AC: 190 AN: 5172

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5195 AN: 10554

Middle Eastern (MID) AF: 0.621 AC: 180 AN: 290

European-Non Finnish (NFE) AF: 0.669 AC: 45447 AN: 67934

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.589 Hom.: 3594

Bravo AF: 0.520

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.55
PhyloP100		-0.43
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: rs10823922; hg19: chr10-74182917;