rs10090288

Positions:

• chr8-17072126-A-C

Variant summary

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

The NM_181723.3(MICU3):​c.567+2407A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,062 control chromosomes in the GnomAD database, including 3,976 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 0.18 (3976 hom., cov: 32)
• Consequence: MICU3 NM_181723.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

MICU3 (HGNC:27820): (mitochondrial calcium uptake family member 3) Predicted to enable calcium ion binding activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Predicted to be located in mitochondrial inner membrane. Predicted to be part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU3	NM_181723.3	c.567+2407A>C		intron_variant		ENST00000318063.10	NP_859074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU3	ENST00000318063.10	c.567+2407A>C		intron_variant		1	NM_181723.3	ENSP00000321455	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27007 AN: 151942 Hom.: 3961 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.178 AC: 27064 AN: 152062 Hom.: 3976 Cov.: 32 AF XY: 0.177 AC XY: 13191 AN XY: 74340

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.168

Alfa AF: 0.0950 Hom.: 2003

Bravo AF: 0.192

Asia WGS AF: 0.219 AC: 758 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.67

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: rs10090288; hg19: chr8-16929635;