chr8-17049616-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181723.3(MICU3):​c.382-14468G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 366,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU3	NM_181723.3	MANE Select	c.382-14468G>T		intron	N/A	NP_859074.1
	MICU3	NM_001349810.2		c.382-14468G>T		intron	N/A	NP_001336739.1
	MICU3	NM_001413217.1		c.382-14468G>T		intron	N/A	NP_001400146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU3	ENST00000318063.10	TSL:1 MANE Select	c.382-14468G>T		intron	N/A	ENSP00000321455.5
	MICU3	ENST00000519044.6	TSL:5	c.382-14468G>T		intron	N/A	ENSP00000427765.2
	MICU3	ENST00000522235.5	TSL:5	n.84-14468G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000273 AC: 1 AN: 366326 Hom.: 0 Cov.: 0 AF XY: 0.00000476 AC XY: 1 AN XY: 210044

African (AFR) AF: 0.00 AC: 0 AN: 10502

American (AMR) AF: 0.00 AC: 0 AN: 36284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11742

East Asian (EAS) AF: 0.00 AC: 0 AN: 13150

South Asian (SAS) AF: 0.00 AC: 0 AN: 66610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2852

European-Non Finnish (NFE) AF: 0.00000522 AC: 1 AN: 191700

Other (OTH) AF: 0.00 AC: 0 AN: 16588

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 19765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		0.053

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;