chr8-17064106-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001413221.1(MICU3):​c.-93T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MICU3 NM_001413221.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029774278).
• BP6: Variant 8-17064106-T-C is Benign according to our data. Variant chr8-17064106-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3126336.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413221.1. 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>C	p.Ile135Thr	missense	Exon 2 of 15	NP_859074.1	Q86XE3
	MICU3	NM_001413221.1		c.-93T>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001400150.1
	MICU3	NM_001349810.2		c.404T>C	p.Ile135Thr	missense	Exon 2 of 15	NP_001336739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICU3	ENST00000318063.10	TSL:1 MANE Select	c.404T>C	p.Ile135Thr	missense	Exon 2 of 15	ENSP00000321455.5	Q86XE3
	MICU3	ENST00000952687.1		c.404T>C	p.Ile135Thr	missense	Exon 2 of 15	ENSP00000622746.1
	MICU3	ENST00000952690.1		c.404T>C	p.Ile135Thr	missense	Exon 2 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.057
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.62
DANN	Benign	0.63
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.022
Sift	Benign	0.75	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.41		Gain of phosphorylation at I135 (P = 0.0168)
MVP		0.088
MPC		0.073
ClinPred		0.020	T
GERP RS		-2.8
PromoterAI		0.013	Neutral
Varity_R		0.078
gMVP		0.19
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;