NM_181723.3:c.567+2407A>C

Variant names:

• chr8-17072126-A-C
• rs10090288
• NM_181723.3:c.567+2407A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181723.3. 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
	MICU3	NM_181723.3	MANE Select	c.567+2407A>C		intron	N/A	NP_859074.1
	MICU3	NM_001349810.2		c.567+2407A>C		intron	N/A	NP_001336739.1
	MICU3	NM_001413217.1		c.567+2407A>C		intron	N/A	NP_001400146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU3	ENST00000318063.10	TSL:1 MANE Select	c.567+2407A>C		intron	N/A	ENSP00000321455.5
	MICU3	ENST00000952687.1		c.567+2407A>C		intron	N/A	ENSP00000622746.1
	MICU3	ENST00000952690.1		c.567+2407A>C		intron	N/A	ENSP00000622749.1

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

African (AFR) AF: 0.397 AC: 16451 AN: 41444

American (AMR) AF: 0.125 AC: 1911 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5164

South Asian (SAS) AF: 0.130 AC: 626 AN: 4820

European-Finnish (FIN) AF: 0.0742 AC: 786 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0723 AC: 4912 AN: 67978

Other (OTH) AF: 0.168 AC: 354 AN: 2110

Alfa AF: 0.114 Hom.: 4859

Bravo AF: 0.192

Asia WGS AF: 0.219 AC: 758 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.67
PhyloP100		-0.081
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: rs10090288; hg19: chr8-16929635;