dbSNP rs3212153: MCUB:c.*733G>A (chr4-109688325-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017918.5(MCUB):c.*733G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,182 control chromosomes in the GnomAD database, including 881 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 0.10 ( 881 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

MCUB
NM_017918.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.294

Publications

10 publications found

Variant links:

Genes affected

MCUB (HGNC:26076): (mitochondrial calcium uniporter dominant negative subunit beta) Predicted to enable calcium channel inhibitor activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Located in mitochondrion and nucleoplasm. Is integral component of mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

MCUB links:

CASP6 (HGNC:1507): (caspase 6) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]

CASP6 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MCUB	NM_017918.5 link	c.*733G>A	3_prime_UTR_variant	Exon 8 of 8	ENST00000394650.7	NP_060388.2	Q9NWR8
MCUB	XM_006714246.4 link	c.*733G>A	3_prime_UTR_variant	Exon 8 of 8		XP_006714309.1
CASP6	XM_047416245.1 link	c.483+6200C>T	intron_variant	Intron 5 of 5		XP_047272201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7 link	c.*733G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_017918.5	ENSP00000378145.4		Q9NWR8

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15347

AN:

152062

Hom.:

879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0919

Gnomad ASJ

AF:

0.0928

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.101

AC:

15345

AN:

152180

Hom.:

881

Cov.:

AF XY:

0.0970

AC XY:

7221

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0554

AC:

2299

AN:

41476

American (AMR)

AF:

0.0919

AC:

1406

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0928

AC:

322

AN:

3470

East Asian (EAS)

AF:

0.0954

AC:

495

AN:

5188

South Asian (SAS)

AF:

0.0593

AC:

286

AN:

4824

European-Finnish (FIN)

AF:

0.102

AC:

1085

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9081

AN:

68010

Other (OTH)

AF:

0.112

AC:

237

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

714

1427

2141

2854

3568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.120

Hom.:

1453

Bravo

AF:

0.101

Asia WGS

AF:

0.0740

AC:

258

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

(source)

DANN

Benign

0.35

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over