rs606231426

Positions:

• chr11-62671804-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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).

• 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

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

Verdict is Uncertain_significance. Variant got 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 id is 161120.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3	c.59T>A	p.Val20Glu	missense_variant	1/2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5	c.-251A>T		5_prime_UTR_variant	1/7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCC3	ENST00000377953.4	c.59T>A	p.Val20Glu	missense_variant	1/2	1	NM_001085372.3	ENSP00000367189	P1
LBHD1	ENST00000354588.8	c.-251A>T		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial complex III deficiency nuclear type 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Benign	-0.30	T
MutationTaster	Benign	0.52	N;N
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;D
Vest4		0.88
MutPred		0.42		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.20
MPC		1.1
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231426; hg19: chr11-62439276;