10-72885804-A-G

Variant names:

• chr10-72885804-A-G
• rs769343948
• NM_138357.3:c.1038A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138357.3(MCU):​c.1038A>G​(p.Gln346Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MCU NM_138357.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1.14 with no splicing effect.

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.1038A>G	p.Gln346Gln	synonymous	Exon 8 of 8	NP_612366.1	Q8NE86-1
	MCU	NM_001270679.2		c.975A>G	p.Gln325Gln	synonymous	Exon 8 of 8	NP_001257608.1	Q8NE86-2
	MCU	NM_001270680.3		c.891A>G	p.Gln297Gln	synonymous	Exon 8 of 8	NP_001257609.1	Q8NE86-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCU	ENST00000373053.8	TSL:1 MANE Select	c.1038A>G	p.Gln346Gln	synonymous	Exon 8 of 8	ENSP00000362144.3	Q8NE86-1
	MCU	ENST00000357157.10	TSL:1	c.975A>G	p.Gln325Gln	synonymous	Exon 8 of 8	ENSP00000349680.6	Q8NE86-2
	MCU	ENST00000857904.1		c.1149A>G	p.Gln383Gln	synonymous	Exon 9 of 9	ENSP00000527963.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461390 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727000

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111648

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.2
DANN	Benign	0.49
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs769343948; hg19: chr10-74645562;