10-72692219-CC-TG

Variant names:

• chr10-72692219-CC-TG
• NM_138357.3:c.68_69delCCinsTG
• MCU p.Ala23Val

Variant summary

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

The NM_138357.3(MCU):​c.68_69delCCinsTG​(p.Ala23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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. A23T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCU NM_138357.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757
• Publications: 0 publications found

Genes affected

MCU (HGNC:23526): (mitochondrial calcium uniporter) Enables calcium channel activity; identical protein binding activity; and uniporter activity. Involved in several processes, including positive regulation of mitochondrial calcium ion concentration; positive regulation of mitochondrial fission; and positive regulation of neutrophil chemotaxis. Acts upstream of or within calcium import into the mitochondrion. Located in mitochondrial inner membrane. Is integral component of mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138357.3. 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
	MCU	NM_138357.3	MANE Select	c.68_69delCCinsTG	p.Ala23Val	missense	N/A	NP_612366.1	Q8NE86-1
	MCU	NM_001270679.2		c.68_69delCCinsTG	p.Ala23Val	missense	N/A	NP_001257608.1	Q8NE86-2
	MCU	NR_073062.2		n.77_78delCCinsTG		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCU	ENST00000373053.8	TSL:1 MANE Select	c.68_69delCCinsTG	p.Ala23Val	missense	N/A	ENSP00000362144.3	Q8NE86-1
	MCU	ENST00000357157.10	TSL:1	c.68_69delCCinsTG	p.Ala23Val	missense	N/A	ENSP00000349680.6	Q8NE86-2
	MCU	ENST00000604372.5	TSL:1	n.68_69delCCinsTG		non_coding_transcript_exon	Exon 1 of 8	ENSP00000474820.1	S4R3W8

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-74451977;