rs10823935

Positions:

• chr10-72566289-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195518.2(MICU1):​c.161+344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,866 control chromosomes in the GnomAD database, including 31,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31611 hom., cov: 30)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU1	NM_001195518.2	c.161+344T>C		intron_variant		ENST00000361114.10	NP_001182447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU1	ENST00000361114.10	c.161+344T>C		intron_variant		1	NM_001195518.2	ENSP00000354415.5

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95504 AN: 151748 Hom.: 31586 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.629 AC: 95571 AN: 151866 Hom.: 31611 Cov.: 30 AF XY: 0.611 AC XY: 45333 AN XY: 74202

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.0420

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.617

Alfa AF: 0.660 Hom.: 4180

Bravo AF: 0.633

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs10823935; hg19: chr10-74326047;