Variant 10-72885820-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_138357.3(MCU):c.1054T>A(p.Ter352Argext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00296 in 1,612,994 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 17 hom. )

Consequence

MCU
NM_138357.3 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.13

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]

MCU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Stoplost variant in NM_138357.3 Downstream stopcodon found after 354 codons.

BP6

Variant 10-72885820-T-A is Benign according to our data. Variant chr10-72885820-T-A is described in ClinVar as [Benign]. Clinvar id is 772945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 368 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCU	NM_138357.3 link	c.1054T>A	p.Ter352Argext*?	stop_lost	8/8	ENST00000373053.8	NP_612366.1	Q8NE86-1
MCU	NM_001270679.2 link	c.991T>A	p.Ter331Argext*?	stop_lost	8/8		NP_001257608.1	Q8NE86-2
MCU	NM_001270680.3 link	c.907T>A	p.Ter303Argext*?	stop_lost	8/8		NP_001257609.1	Q8NE86-3
MCU	NR_073062.2 link	n.1228T>A		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCU	ENST00000373053.8 link	c.1054T>A	p.Ter352Argext*?	stop_lost	8/8	1	NM_138357.3	ENSP00000362144.3		Q8NE86-1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

368

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00302

AC:

758

AN:

251052

Hom.:

AF XY:

0.00307

AC XY:

417

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00302

AC:

4406

AN:

1460692

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

2097

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000870

Gnomad4 FIN exome

AF:

0.00959

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00242

AC:

368

AN:

152302

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00287

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00188

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00315

AC:

382

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00308

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.86

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.97

Vest4

0.38

GERP RS

5.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over