rs606231426

Variant names:

• chr11-62671804-T-A
• rs606231426
• NM_001085372.3:c.59T>A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001085372.3(UQCC3):​c.59T>A​(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. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). 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: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.68
• Publications: 7 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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865
• PP5: Variant 11-62671804-T-A is Pathogenic according to our data. Variant chr11-62671804-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 161120.Status of the report is no_assertion_criteria_provided, 0 stars.

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.59T>A	p.Val20Glu	missense	Exon 1 of 2	NP_001078841.1
	LBHD1	NM_024099.5	MANE Select	c.-251A>T		5_prime_UTR	Exon 1 of 7	NP_077004.2
	LBHD1	NM_001394599.1		c.-57A>T		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.59T>A	p.Val20Glu	missense	Exon 1 of 2	ENSP00000367189.3
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-251A>T		5_prime_UTR	Exon 1 of 7	ENSP00000346600.3
	UQCC3	ENST00000531323.1	TSL:3	c.59T>A	p.Val20Glu	missense	Exon 2 of 3	ENSP00000432692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Mitochondrial complex III deficiency nuclear type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.30	T
PhyloP100		1.7
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.88
MutPred		0.42		Gain of solvent accessibility (P = 0.0145)
MVP		0.20
MPC		1.1
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		-0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.39
Mutation Taster		=28/72	disease causing (ClinVar)

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: rs606231426; hg19: chr11-62439276;