Genetic Variant MCUR1:c.1025-40A>G (chr6-13790904-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031713.4(MCUR1):c.1025-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,446,734 control chromosomes in the GnomAD database, including 1,949 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 0.061 ( 461 hom., cov: 31)

Exomes 𝑓: 0.043 ( 1488 hom. )

Consequence

MCUR1
NM_001031713.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

4 publications found

Variant links:

Genes affected

MCUR1 (HGNC:21097): (mitochondrial calcium uniporter regulator 1) Involved in calcium import into the mitochondrion and positive regulation of mitochondrial calcium ion concentration. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

MCUR1 links:

ENSG00000307512 (HGNC:):

ENSG00000307512 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031713.4. 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
	MCUR1	NM_001031713.4	MANE Select	c.1025-40A>G		intron	N/A	NP_001026883.1	Q96AQ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCUR1	ENST00000379170.9	TSL:1 MANE Select	c.1025-40A>G	intron	N/A	ENSP00000368468.3	Q96AQ8-1
MCUR1	ENST00000886884.1		c.971-40A>G	intron	N/A	ENSP00000556943.1
MCUR1	ENST00000886881.1		c.953-40A>G	intron	N/A	ENSP00000556940.1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9314

AN:

152138

Hom.:

459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.0181

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.00707

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0390

Gnomad OTH

AF:

0.0512

GnomAD2 exomes

AF:

0.0417

AC:

9103

AN:

218314

AF XY:

0.0415

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0362

Gnomad EAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.00833

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0430

AC:

55600

AN:

1294478

Hom.:

1488

Cov.:

AF XY:

0.0431

AC XY:

28055

AN XY:

651228

show subpopulations

African (AFR)

AF:

0.132

AC:

3733

AN:

28352

American (AMR)

AF:

0.0289

AC:

1017

AN:

35240

Ashkenazi Jewish (ASJ)

AF:

0.0327

AC:

771

AN:

23558

East Asian (EAS)

AF:

0.0230

AC:

874

AN:

37970

South Asian (SAS)

AF:

0.0532

AC:

4121

AN:

77414

European-Finnish (FIN)

AF:

0.00787

AC:

414

AN:

52632

Middle Eastern (MID)

AF:

0.0539

AC:

289

AN:

5366

European-Non Finnish (NFE)

AF:

0.0427

AC:

41789

AN:

979586

Other (OTH)

AF:

0.0477

AC:

2592

AN:

54360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2415

4830

7245

9660

12075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1598

3196

4794

6392

7990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0613

AC:

9334

AN:

152256

Hom.:

461

Cov.:

AF XY:

0.0593

AC XY:

4415

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.130

AC:

5409

AN:

41544

American (AMR)

AF:

0.0366

AC:

559

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

125

AN:

3468

East Asian (EAS)

AF:

0.0181

AC:

AN:

5182

South Asian (SAS)

AF:

0.0615

AC:

297

AN:

4826

European-Finnish (FIN)

AF:

0.00707

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0390

AC:

2650

AN:

68016

Other (OTH)

AF:

0.0511

AC:

108

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

428

857

1285

1714

2142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0496

Hom.:

378

Bravo

AF:

0.0642

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.5

(source)

DANN

Benign

0.81

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over