rs2014286

Variant names:

• chr8-17049616-G-A
• rs2014286
• NM_181723.3:c.382-14468G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.88).
• 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 rank	MANE	Protein	UniProt
MICU3	NM_181723.3	c.382-14468G>A		intron_variant	Intron 1 of 14	ENST00000318063.10	NP_859074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICU3	ENST00000318063.10	c.382-14468G>A		intron_variant	Intron 1 of 14	1	NM_181723.3	ENSP00000321455.5
MICU3	ENST00000519044.6	c.382-14468G>A		intron_variant	Intron 1 of 13	5		ENSP00000427765.2
MICU3	ENST00000522235.5	n.84-14468G>A		intron_variant	Intron 1 of 2	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

GnomAD2 exomes AF: 0.235 AC: 53699 AN: 228426 AF XY: 0.218

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 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

African (AFR) AF: 0.653 AC: 6855 AN: 10492

American (AMR) AF: 0.273 AC: 9913 AN: 36268

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 1645 AN: 11738

East Asian (EAS) AF: 0.602 AC: 7903 AN: 13136

South Asian (SAS) AF: 0.144 AC: 9604 AN: 66560

European-Finnish (FIN) AF: 0.118 AC: 1988 AN: 16892

Middle Eastern (MID) AF: 0.166 AC: 473 AN: 2852

European-Non Finnish (NFE) AF: 0.152 AC: 29039 AN: 191576

Other (OTH) AF: 0.201 AC: 3336 AN: 16570

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

African (AFR) AF: 0.655 AC: 27118 AN: 41430

American (AMR) AF: 0.251 AC: 3830 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3066 AN: 5146

South Asian (SAS) AF: 0.162 AC: 784 AN: 4826

European-Finnish (FIN) AF: 0.117 AC: 1235 AN: 10584

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.153 AC: 10383 AN: 67978

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.214 Hom.: 19765

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
PhyloP100		0.053
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: rs2014286; hg19: chr8-16907125;