10-72814932-A-T

Variant names:

• chr10-72814932-A-T
• rs11000419
• NM_138357.3:c.151-19427A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138357.3(MCU):​c.151-19427A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,906 control chromosomes in the GnomAD database, including 19,865 homozygotes. 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: 𝑓 0.45 (19865 hom., cov: 33)
• Consequence: MCU NM_138357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

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.151-19427A>T		intron	N/A	NP_612366.1	Q8NE86-1
	MCU	NM_001270679.2		c.151-19427A>T		intron	N/A	NP_001257608.1	Q8NE86-2
	MCU	NM_001270680.3		c.4-19427A>T		intron	N/A	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.151-19427A>T		intron	N/A	ENSP00000362144.3	Q8NE86-1
	MCU	ENST00000357157.10	TSL:1	c.151-19427A>T		intron	N/A	ENSP00000349680.6	Q8NE86-2
	MCU	ENST00000604372.5	TSL:1	n.*157-19427A>T		intron	N/A	ENSP00000474820.1	S4R3W8

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69110 AN: 151788 Hom.: 19869 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.455 AC: 69094 AN: 151906 Hom.: 19865 Cov.: 33 AF XY: 0.443 AC XY: 32892 AN XY: 74248

African (AFR) AF: 0.141 AC: 5851 AN: 41546

American (AMR) AF: 0.454 AC: 6924 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1913 AN: 3466

East Asian (EAS) AF: 0.0355 AC: 184 AN: 5186

South Asian (SAS) AF: 0.433 AC: 2093 AN: 4830

European-Finnish (FIN) AF: 0.490 AC: 5139 AN: 10494

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45218 AN: 67822

Other (OTH) AF: 0.490 AC: 1033 AN: 2110

Alfa AF: 0.548 Hom.: 3127

Bravo AF: 0.437

Asia WGS AF: 0.209 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs11000419; hg19: chr10-74574690;