chr8-17064106-T-G

Variant names:

• chr8-17064106-T-G
• rs1178352566
• NM_181723.3:c.404T>G

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.404T>G​(p.Ile135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. I135T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MICU3 NM_181723.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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: 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 (MetaRNN=0.03552851).

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.404T>G	p.Ile135Ser	missense	Exon 2 of 15	NP_859074.1	Q86XE3
	MICU3	NM_001349810.2		c.404T>G	p.Ile135Ser	missense	Exon 2 of 15	NP_001336739.1
	MICU3	NM_001413217.1		c.404T>G	p.Ile135Ser	missense	Exon 2 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.404T>G	p.Ile135Ser	missense	Exon 2 of 15	ENSP00000321455.5	Q86XE3
	MICU3	ENST00000952687.1		c.404T>G	p.Ile135Ser	missense	Exon 2 of 15	ENSP00000622746.1
	MICU3	ENST00000952690.1		c.404T>G	p.Ile135Ser	missense	Exon 2 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459570 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726032

African (AFR) AF: 0.0000299 AC: 1 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110772

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

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	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.030
Sift	Benign	0.62	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.23
MutPred		0.45		Gain of disorder (P = 0.0088)
MVP		0.10
MPC		0.085
ClinPred		0.035	T
GERP RS		-2.8
PromoterAI		0.0048	Neutral
Varity_R		0.12
gMVP		0.38
Mutation Taster		=96/4	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: rs1178352566; hg19: chr8-16921615;