rs2014286

Positions:

• chr8-17049616-G-A
• chr8-17049616-G-T

Variant summary

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

The NM_181723.3(MICU3):​c.382-14468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 518,112 control chromosomes in the GnomAD database, including 21,168 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 0.31 (11472 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9696 hom.)
• Consequence: MICU3 NM_181723.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU3	NM_181723.3	c.382-14468G>A		intron_variant		ENST00000318063.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU3	ENST00000318063.10	c.382-14468G>A		intron_variant		1	NM_181723.3	P1
MICU3	ENST00000522235.5	n.84-14468G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47573 AN: 151912 Hom.: 11446 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.235 AC: 53699 AN: 228426 Hom.: 9571 AF XY: 0.218 AC XY: 27500 AN XY: 126254

Gnomad AFR exome AF: 0.670

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.193 AC: 70756 AN: 366084 Hom.: 9696 Cov.: 0 AF XY: 0.183 AC XY: 38396 AN XY: 209906

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.313 AC: 47648 AN: 152028 Hom.: 11472 Cov.: 32 AF XY: 0.309 AC XY: 22991 AN XY: 74294

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.278

Alfa AF: 0.179 Hom.: 6105

Bravo AF: 0.343

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.65

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: rs2014286; hg19: chr8-16907125;