10-72368386-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001195518.2(MICU1):c.1271-31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,601,568 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (30 hom.)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.53

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-72368386-A-C is Benign according to our data. Variant chr10-72368386-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1210618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00106 (162/152342) while in subpopulation SAS AF= 0.0135 (65/4828). AF 95% confidence interval is 0.0108. There are 3 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.1271-31T>G		intron_variant		ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.1271-31T>G		intron_variant		1	NM_001195518.2	P4

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 160 AN: 152224 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00276 AC: 680 AN: 246414 Hom.: 8 AF XY: 0.00321 AC XY: 430 AN XY: 133870

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000581

Gnomad ASJ exome AF: 0.00629

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.0154

Gnomad FIN exome AF: 0.0000484

Gnomad NFE exome AF: 0.000917

Gnomad OTH exome AF: 0.00349

GnomAD4 exome AF: 0.00157 AC: 2277 AN: 1449226 Hom.: 30 Cov.: 31 AF XY: 0.00199 AC XY: 1426 AN XY: 718300

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000628

Gnomad4 ASJ exome AF: 0.00580

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.0000575

Gnomad4 NFE exome AF: 0.000534

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00106 AC: 162 AN: 152342 Hom.: 3 Cov.: 31 AF XY: 0.00114 AC XY: 85 AN XY: 74500

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.000782

Asia WGS AF: 0.00462 AC: 18 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	17
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149949660; hg19: chr10-74128144;