rs915432

Variant names:

• chr10-72475059-T-C
• rs915432
• NM_001195518.2:c.933+41A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-72475059-T-C
• chr10-72475059-T-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.933+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,550,644 control chromosomes in the GnomAD database, including 345,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35417 hom., cov: 32)
  • Exomes 𝑓: 0.66 (309627 hom.)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.440
• Publications: 7 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):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• proximal myopathy with extrapyramidal signs

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-72475059-T-C is Benign according to our data. Variant chr10-72475059-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	NM_001195518.2	MANE Select	c.933+41A>G		intron	N/A	NP_001182447.1	Q9BPX6-1
	MICU1	NM_001441218.1		c.1164+41A>G		intron	N/A	NP_001428147.1
	MICU1	NM_001441219.1		c.1101+41A>G		intron	N/A	NP_001428148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU1	ENST00000361114.10	TSL:1 MANE Select	c.933+41A>G		intron	N/A	ENSP00000354415.5	Q9BPX6-1
	MICU1	ENST00000964210.1		c.1164+41A>G		intron	N/A	ENSP00000634269.1
	MICU1	ENST00000897977.1		c.1101+41A>G		intron	N/A	ENSP00000568036.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101724 AN: 151970 Hom.: 35382 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.654

GnomAD2 exomes AF: 0.588 AC: 111844 AN: 190168 AF XY: 0.592

Gnomad AFR exome AF: 0.826

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.583

Gnomad EAS exome AF: 0.272

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.658 AC: 920897 AN: 1398556 Hom.: 309627 Cov.: 24 AF XY: 0.656 AC XY: 454024 AN XY: 692024

African (AFR) AF: 0.826 AC: 26861 AN: 32500

American (AMR) AF: 0.461 AC: 17631 AN: 38284

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 14108 AN: 24316

East Asian (EAS) AF: 0.267 AC: 10231 AN: 38356

South Asian (SAS) AF: 0.541 AC: 42597 AN: 78678

European-Finnish (FIN) AF: 0.526 AC: 26748 AN: 50822

Middle Eastern (MID) AF: 0.703 AC: 3925 AN: 5582

European-Non Finnish (NFE) AF: 0.692 AC: 741418 AN: 1071798

Other (OTH) AF: 0.642 AC: 37378 AN: 58220

GnomAD4 genome AF: 0.669 AC: 101803 AN: 152088 Hom.: 35417 Cov.: 32 AF XY: 0.653 AC XY: 48526 AN XY: 74320

African (AFR) AF: 0.821 AC: 34070 AN: 41522

American (AMR) AF: 0.546 AC: 8345 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5164

South Asian (SAS) AF: 0.514 AC: 2479 AN: 4820

European-Finnish (FIN) AF: 0.500 AC: 5285 AN: 10564

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46136 AN: 67966

Other (OTH) AF: 0.648 AC: 1367 AN: 2108

Alfa AF: 0.650 Hom.: 9211

Bravo AF: 0.679

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	7.7
DANN	Benign	0.30
PhyloP100		0.44
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: rs915432; hg19: chr10-74234817; COSMIC: COSV63144688; COSMIC: COSV63144688;