rs10504961

Variant names:

• chr8-96227901-C-T
• rs10504961
• NM_006294.5:c.*3154G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006294.5(UQCRB):​c.*3154G>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 0.445 in 453,846 control chromosomes in the GnomAD database, including 46,486 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 0.46 (16300 hom., cov: 33)
  • Exomes 𝑓: 0.44 (30186 hom.)
• Consequence: UQCRB NM_006294.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 11 publications found

Genes affected

UQCRB (HGNC:12582): (ubiquinol-cytochrome c reductase binding protein) This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 2011]

UQCRB Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency nuclear type 3

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRB	NM_006294.5	c.*3154G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000287022.10	NP_006285.1
UQCRB	NR_045639.2	n.3795G>A		non_coding_transcript_exon_variant	Exon 5 of 5
UQCRB	NM_001254752.2	c.*3204G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001241681.1
UQCRB	NM_001199975.3	c.*3154G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001186904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRB	ENST00000287022.10	c.*3154G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_006294.5	ENSP00000287022.5

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69425 AN: 151952 Hom.: 16283 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.407 AC: 53040 AN: 130448 AF XY: 0.414

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.473

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.439 AC: 132417 AN: 301776 Hom.: 30186 Cov.: 0 AF XY: 0.437 AC XY: 75233 AN XY: 171988

African (AFR) AF: 0.489 AC: 4186 AN: 8554

American (AMR) AF: 0.316 AC: 8609 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 5042 AN: 10786

East Asian (EAS) AF: 0.182 AC: 1679 AN: 9210

South Asian (SAS) AF: 0.400 AC: 23866 AN: 59646

European-Finnish (FIN) AF: 0.474 AC: 5857 AN: 12364

Middle Eastern (MID) AF: 0.462 AC: 531 AN: 1150

European-Non Finnish (NFE) AF: 0.481 AC: 76424 AN: 158752

Other (OTH) AF: 0.443 AC: 6223 AN: 14040

GnomAD4 genome AF: 0.457 AC: 69481 AN: 152070 Hom.: 16300 Cov.: 33 AF XY: 0.453 AC XY: 33674 AN XY: 74354

African (AFR) AF: 0.492 AC: 20413 AN: 41468

American (AMR) AF: 0.373 AC: 5706 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1712 AN: 3470

East Asian (EAS) AF: 0.191 AC: 988 AN: 5176

South Asian (SAS) AF: 0.362 AC: 1750 AN: 4828

European-Finnish (FIN) AF: 0.448 AC: 4725 AN: 10558

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32644 AN: 67974

Other (OTH) AF: 0.445 AC: 936 AN: 2102

Alfa AF: 0.480 Hom.: 5680

Bravo AF: 0.449

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.52
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10504961; hg19: chr8-97240129;