8-17027471-G-C

Variant names:

• chr8-17027471-G-C
• rs781023389
• NM_181723.3:c.192G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_181723.3(MICU3):​c.192G>C​(p.Trp64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000728 in 1,291,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W64S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: MICU3 NM_181723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• 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]

ENSG00000289225 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.192G>C	p.Trp64Cys	missense	Exon 1 of 15	NP_859074.1	Q86XE3
	MICU3	NM_001349810.2		c.192G>C	p.Trp64Cys	missense	Exon 1 of 15	NP_001336739.1
	MICU3	NM_001413217.1		c.192G>C	p.Trp64Cys	missense	Exon 1 of 14	NP_001400146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU3	ENST00000318063.10	TSL:1 MANE Select	c.192G>C	p.Trp64Cys	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
	MICU3	ENST00000952687.1		c.192G>C	p.Trp64Cys	missense	Exon 1 of 15	ENSP00000622746.1
	MICU3	ENST00000952690.1		c.192G>C	p.Trp64Cys	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151926 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 85 AN: 1139494 Hom.: 0 Cov.: 33 AF XY: 0.0000694 AC XY: 38 AN XY: 547744

African (AFR) AF: 0.0000858 AC: 2 AN: 23310

American (AMR) AF: 0.000115 AC: 1 AN: 8680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15318

East Asian (EAS) AF: 0.0000369 AC: 1 AN: 27076

South Asian (SAS) AF: 0.0000910 AC: 3 AN: 32956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26348

Middle Eastern (MID) AF: 0.000639 AC: 2 AN: 3130

European-Non Finnish (NFE) AF: 0.0000742 AC: 71 AN: 956624

Other (OTH) AF: 0.000109 AC: 5 AN: 46052

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151926 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74210

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.55		Gain of disorder (P = 0.0339)
MVP		0.45
MPC		2.4
ClinPred		0.88	D
GERP RS		3.2
PromoterAI		-0.028	Neutral
Varity_R		0.37
gMVP		0.42
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs781023389; hg19: chr8-16884980;