rs3212153

chr4-109688325-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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]

CASP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
MCUB	NM_017918.5	c.*733G>A		3_prime_UTR_variant	8/8	ENST00000394650.7
MCUB	XM_006714246.4	c.*733G>A		3_prime_UTR_variant	8/8
CASP6	XM_047416245.1	c.483+6200C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCUB	ENST00000394650.7	c.*733G>A		3_prime_UTR_variant	8/8	1	NM_017918.5	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15347 AN: 152062 Hom.: 879 Cov.: 33

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: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.101 AC: 15345 AN: 152180 Hom.: 881 Cov.: 33 AF XY: 0.0970 AC XY: 7221 AN XY: 74426

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.0954

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.112

Alfa AF: 0.123 Hom.: 1180

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
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs3212153; hg19: chr4-110609481;