11-62671975-G-C

Variant names:

• chr11-62671975-G-C
• rs199794771
• NM_001085372.3:c.143G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001085372.3(UQCC3):​c.143G>C​(p.Arg48Thr) 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 benign outcome for this variant. 13/18 in silico tools predict 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: 32)
• Consequence: UQCC3 NM_001085372.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06307262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCC3	NM_001085372.3	c.143G>C	p.Arg48Thr	missense_variant	Exon 2 of 2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5	c.-422C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCC3	ENST00000377953.4	c.143G>C	p.Arg48Thr	missense_variant	Exon 2 of 2	1	NM_001085372.3	ENSP00000367189.3
LBHD1	ENST00000354588.8	c.-422C>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_024099.5	ENSP00000346600.3
UQCC3	ENST00000531323.1	c.143G>C	p.Arg48Thr	missense_variant	Exon 3 of 3	3		ENSP00000432692.1
LBHD1	ENST00000528862.2	c.93+152C>G		intron_variant	Intron 1 of 2	3		ENSP00000434489.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.62
DANN	Benign	0.60
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.031
Sift	Benign	0.43	T;T
Sift4G	Benign	0.073	T;T
Polyphen		0.36	B;B
Vest4		0.14
MutPred		0.15		Gain of phosphorylation at R48 (P = 0.0123);Gain of phosphorylation at R48 (P = 0.0123);
MVP		0.048
MPC		0.55
ClinPred		0.21	T
GERP RS		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.088

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199794771; hg19: chr11-62439447;