8-96235513-GGC-CGA

Variant names:

• chr8-96235513-GGC-CGA
• NM_006294.5:c.16_18delGCCinsTCG
• UQCRB p.Ala6Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006294.5(UQCRB):​c.16_18delGCCinsTCG​(p.Ala6Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UQCRB NM_006294.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 0 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-AS1 (HGNC:55521): (UQCRB antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006294.5. 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	NM_006294.5	MANE Select	c.16_18delGCCinsTCG	p.Ala6Ser	missense splice_region	N/A	NP_006285.1	P14927-1
	UQCRB	NM_001254752.2		c.16_18delGCCinsTCG	p.Ala6Ser	missense splice_region	N/A	NP_001241681.1	P14927-2
	UQCRB	NM_001199975.3		c.-195_-193delGCCinsTCG		splice_region	Exon 1 of 5	NP_001186904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.16_18delGCCinsTCG	p.Ala6Ser	missense splice_region	N/A	ENSP00000287022.5	P14927-1
	UQCRB	ENST00000517603.5	TSL:1	n.16_18delGCCinsTCG		splice_region non_coding_transcript_exon	Exon 1 of 5	ENSP00000430672.1	E5RIT7
	UQCRB	ENST00000518876.1	TSL:1	n.30_32delGCCinsTCG		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-97247741;