13-21566847-T-A

Position:

• chr13-21566847-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152726.3(MICU2):​c.308A>T​(p.Tyr103Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MICU2 NM_152726.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

Genes affected

MICU2 (HGNC:31830): (mitochondrial calcium uptake 2) Enables protein heterodimerization activity. Involved in calcium import into the mitochondrion and negative regulation of mitochondrial calcium ion concentration. Located in mitochondrial inner membrane and mitochondrial intermembrane space. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU2	NM_152726.3	c.308A>T	p.Tyr103Phe	missense_variant	2/12	ENST00000382374.9	NP_689939.1
MICU2	XM_047430141.1	c.308A>T	p.Tyr103Phe	missense_variant	2/11		XP_047286097.1
MICU2	XM_047430142.1	c.38A>T	p.Tyr13Phe	missense_variant	3/13		XP_047286098.1
MICU2	XM_047430143.1	c.308A>T	p.Tyr103Phe	missense_variant	2/10		XP_047286099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICU2	ENST00000382374.9	c.308A>T	p.Tyr103Phe	missense_variant	2/12	1	NM_152726.3	ENSP00000371811.4
MICU2	ENST00000468222.2	c.308A>T	p.Tyr103Phe	missense_variant	2/9	5		ENSP00000431792.2
MICU2	ENST00000469058.1	n.400A>T		non_coding_transcript_exon_variant	3/9	5
MICU2	ENST00000476895.5	n.286A>T		non_coding_transcript_exon_variant	3/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.308A>T (p.Y103F) alteration is located in exon 2 (coding exon 2) of the MICU2 gene. This alteration results from a A to T substitution at nucleotide position 308, causing the tyrosine (Y) at amino acid position 103 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.56
Sift	Benign	0.20	T;T
Sift4G	Benign	0.13	T;.
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.64		Loss of phosphorylation at Y103 (P = 0.0143);Loss of phosphorylation at Y103 (P = 0.0143);
MVP		0.48
MPC		0.56
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.53
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-22140986;