10-72860513-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138357.3(MCU):​c.482G>A​(p.Arg161Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,613,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MCU
NM_138357.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.032541305).
BS2
High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MCUNM_138357.3 linkc.482G>A p.Arg161Gln missense_variant 4/8 ENST00000373053.8 NP_612366.1 Q8NE86-1
MCUNM_001270679.2 linkc.482G>A p.Arg161Gln missense_variant 4/8 NP_001257608.1 Q8NE86-2
MCUNM_001270680.3 linkc.335G>A p.Arg112Gln missense_variant 4/8 NP_001257609.1 Q8NE86-3
MCUNR_073062.2 linkn.656G>A non_coding_transcript_exon_variant 6/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCUENST00000373053.8 linkc.482G>A p.Arg161Gln missense_variant 4/81 NM_138357.3 ENSP00000362144.3 Q8NE86-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152030
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251060
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1460956
Hom.:
0
Cov.:
29
AF XY:
0.0000165
AC XY:
12
AN XY:
726810
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 10, 2023The c.482G>A (p.R161Q) alteration is located in exon 4 (coding exon 4) of the MCU gene. This alteration results from a G to A substitution at nucleotide position 482, causing the arginine (R) at amino acid position 161 to be replaced by a glutamine (Q). 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
0.066
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.54
CADD
Uncertain
23
DANN
Benign
0.37
DEOGEN2
Benign
0.0081
T;.;.;.
Eigen
Benign
-0.19
Eigen_PC
Benign
0.056
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.033
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.26
N;N;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.050
N;N;N;.
REVEL
Benign
0.058
Sift
Benign
0.80
T;T;T;.
Sift4G
Benign
0.94
T;T;T;T
Polyphen
0.0090
B;B;B;.
Vest4
0.28
MVP
0.082
MPC
0.73
ClinPred
0.086
T
GERP RS
5.7
Varity_R
0.24
gMVP
0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146047894; hg19: chr10-74620271; API