8-96235630-C-T

Variant names:

• chr8-96235630-C-T
• rs73698550
• ENST00000520575.2:n.271+69C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000520575.2(UQCRB-AS1):​n.271+69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: UQCRB-AS1 ENST00000520575.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 1 publications found

Genes affected

UQCRB-AS1 (HGNC:55521): (UQCRB antisense RNA 1)

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520575.2. 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
	UQCRB-AS1	NR_183274.1		n.269+69C>T		intron	N/A
	UQCRB-AS1	NR_183275.1		n.269+69C>T		intron	N/A
	UQCRB	NM_006294.5	MANE Select	c.-100G>A		upstream_gene	N/A	NP_006285.1	P14927-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB-AS1	ENST00000520575.2	TSL:2	n.271+69C>T		intron	N/A
	UQCRB-AS1	ENST00000727541.1		n.574+69C>T		intron	N/A
	UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.-100G>A		upstream_gene	N/A	ENSP00000287022.5	P14927-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245472 AF XY: 0.00000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344750 Hom.: 0 Cov.: 21 AF XY: 0.00000148 AC XY: 1 AN XY: 675758

African (AFR) AF: 0.00 AC: 0 AN: 31022

American (AMR) AF: 0.00 AC: 0 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006832

Other (OTH) AF: 0.00 AC: 0 AN: 56298

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.99
DANN	Benign	0.96
PhyloP100		-0.33
PromoterAI		0.027	Neutral

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: rs73698550; hg19: chr8-97247858;