11-62671813-C-T

Variant names:

• chr11-62671813-C-T
• rs1449562810
• NM_001085372.3:c.68C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085372.3(UQCC3):​c.68C>T​(p.Ala23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A23G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UQCC3 NM_001085372.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11884147).

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.68C>T	p.Ala23Val	missense	Exon 1 of 2	NP_001078841.1	Q6UW78
	LBHD1	NM_024099.5	MANE Select	c.-260G>A		5_prime_UTR	Exon 1 of 7	NP_077004.2
	LBHD1	NM_001394599.1		c.-66G>A		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.68C>T	p.Ala23Val	missense	Exon 1 of 2	ENSP00000367189.3	Q6UW78
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-260G>A		5_prime_UTR	Exon 1 of 7	ENSP00000346600.3	Q9BQE6-2
	UQCC3	ENST00000531323.1	TSL:3	c.68C>T	p.Ala23Val	missense	Exon 2 of 3	ENSP00000432692.1	Q6UW78

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.45
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.026
Sift	Benign	0.27	T
Sift4G	Benign	0.78	T
Polyphen		0.83	P
Vest4		0.38
MutPred		0.35		Loss of phosphorylation at Y22 (P = 0.1828)
MVP		0.081
MPC		0.88
ClinPred		0.92	D
GERP RS		2.6
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.11
Mutation Taster		=97/3	polymorphism

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: rs1449562810; hg19: chr11-62439285; COSMIC: COSV99583315; COSMIC: COSV99583315;