11-62671804-TG-AA

Variant names:

• chr11-62671804-TG-AA
• NM_001085372.3:c.59_60delTGinsAA
• UQCC3 p.Val20Glu

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1

The NM_001085372.3(UQCC3):​c.59_60delTGinsAA​(p.Val20Glu) variant causes a missense 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 Pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V20L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCC3 NM_001085372.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

Genes affected

UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_001085372.3 (UQCC3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085372.3. 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
	UQCC3	NM_001085372.3	MANE Select	c.59_60delTGinsAA	p.Val20Glu	missense	N/A	NP_001078841.1	Q6UW78
	LBHD1	NM_024099.5	MANE Select	c.-252_-251delCAinsTT		5_prime_UTR	Exon 1 of 7	NP_077004.2
	LBHD1	NM_001394599.1		c.-58_-57delCAinsTT		5_prime_UTR	Exon 1 of 7	NP_001381528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC3	ENST00000377953.4	TSL:1 MANE Select	c.59_60delTGinsAA	p.Val20Glu	missense	N/A	ENSP00000367189.3	Q6UW78
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-252_-251delCAinsTT		5_prime_UTR	Exon 1 of 7	ENSP00000346600.3	Q9BQE6-2
	UQCC3	ENST00000531323.1	TSL:3	c.59_60delTGinsAA	p.Val20Glu	missense	N/A	ENSP00000432692.1	Q6UW78

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

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: chr11-62439276;