chr8-17032501-T-C

Variant names:

• chr8-17032501-T-C
• rs2106011
• NM_181723.3:c.381+4841T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_181723.3(MICU3):​c.381+4841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 152,338 control chromosomes in the GnomAD database, including 38 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 0.018 (38 hom., cov: 33)
• Consequence: MICU3 NM_181723.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 0 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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2676/152338) while in subpopulation NFE AF = 0.0289 (1966/68026). AF 95% confidence interval is 0.0278. There are 38 homozygotes in GnomAd4. There are 1256 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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.381+4841T>C		intron	N/A	NP_859074.1
	MICU3	NM_001349810.2		c.381+4841T>C		intron	N/A	NP_001336739.1
	MICU3	NM_001413217.1		c.381+4841T>C		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.381+4841T>C		intron	N/A	ENSP00000321455.5
	MICU3	ENST00000519044.6	TSL:5	c.381+4841T>C		intron	N/A	ENSP00000427765.2
	MICU3	ENST00000522235.5	TSL:5	n.83+4841T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2678 AN: 152220 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0176 AC: 2676 AN: 152338 Hom.: 38 Cov.: 33 AF XY: 0.0169 AC XY: 1256 AN XY: 74496

African (AFR) AF: 0.00493 AC: 205 AN: 41584

American (AMR) AF: 0.00863 AC: 132 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.0250 AC: 266 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0289 AC: 1966 AN: 68026

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0225 Hom.: 16

Bravo AF: 0.0155

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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: rs2106011; hg19: chr8-16890010;