22-29767463-C-A

Variant names:

• chr22-29767463-C-A
• rs753668573
• NM_013387.4:c.65C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013387.4(UQCR10):​c.65C>A​(p.Ala22Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A22V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UQCR10 NM_013387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92
• Publications: 0 publications found

Genes affected

UQCR10 (HGNC:30863): (ubiquinol-cytochrome c reductase, complex III subunit X) UCRC is a subunit of mitochondrial complex III (ubiquinol-cytochrome c reductase; EC 1.10.2.2), which forms the middle segment of the respiratory chain of the inner mitochondrial membrane (Schagger et al., 1995 [PubMed 8592474]).[supplied by OMIM, Mar 2008]

ENSG00000287967 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013387.4. 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
	UQCR10	NM_013387.4	MANE Select	c.65C>A	p.Ala22Asp	missense	Exon 1 of 2	NP_037519.2
	UQCR10	NM_001003684.2		c.65C>A	p.Ala22Asp	missense	Exon 1 of 2	NP_001003684.1	Q9UDW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCR10	ENST00000330029.6	TSL:1 MANE Select	c.65C>A	p.Ala22Asp	missense	Exon 1 of 2	ENSP00000332887.6	Q9UDW1-1
	UQCR10	ENST00000401406.3	TSL:1	c.65C>A	p.Ala22Asp	missense	Exon 1 of 2	ENSP00000384962.3	Q9UDW1-2
	UQCR10	ENST00000894363.1		c.65C>A	p.Ala22Asp	missense	Exon 1 of 2	ENSP00000564422.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461676 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727114

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: 26136

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.23	T
PhyloP100		5.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.76		Gain of relative solvent accessibility (P = 0.09)
MVP		0.42
MPC		1.2
ClinPred		0.99	D
GERP RS		5.7
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.97
gMVP		0.92
Mutation Taster		=27/73	disease causing

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: rs753668573; hg19: chr22-30163452;