8-17027649-G-C

Variant names:

• chr8-17027649-G-C
• rs1007657526
• NM_181723.3:c.370G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181723.3(MICU3):​c.370G>C​(p.Ala124Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000384 in 1,300,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A124T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: MICU3 NM_181723.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.35
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.370G>C	p.Ala124Pro	missense	Exon 1 of 15	NP_859074.1	Q86XE3
	MICU3	NM_001349810.2		c.370G>C	p.Ala124Pro	missense	Exon 1 of 15	NP_001336739.1
	MICU3	NM_001413217.1		c.370G>C	p.Ala124Pro	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.370G>C	p.Ala124Pro	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
	MICU3	ENST00000952687.1		c.370G>C	p.Ala124Pro	missense	Exon 1 of 15	ENSP00000622746.1
	MICU3	ENST00000952690.1		c.370G>C	p.Ala124Pro	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000261 AC: 3 AN: 1148662 Hom.: 0 Cov.: 34 AF XY: 0.00000181 AC XY: 1 AN XY: 552336

African (AFR) AF: 0.00 AC: 0 AN: 23374

American (AMR) AF: 0.00 AC: 0 AN: 9402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15742

East Asian (EAS) AF: 0.00 AC: 0 AN: 26948

South Asian (SAS) AF: 0.00 AC: 0 AN: 37816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3132

European-Non Finnish (NFE) AF: 0.00000313 AC: 3 AN: 959896

Other (OTH) AF: 0.00 AC: 0 AN: 46472

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.35		Gain of glycosylation at A124 (P = 0.0224)
MVP		0.48
MPC		1.5
ClinPred		0.94	D
GERP RS		3.2
PromoterAI		0.049	Neutral
Varity_R		0.41
gMVP		0.58
Mutation Taster		=71/29	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: rs1007657526; hg19: chr8-16885158;