rs4911494

Positions:

• chr20-35384111-C-A
• chr20-35384111-C-G
• chr20-35384111-C-T

Variant summary

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

The NM_018244.5(UQCC1):​c.152G>T​(p.Arg51Leu) 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. 15/21 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. R51Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

Genes affected

UQCC1 (HGNC:15891): (ubiquinol-cytochrome c reductase complex assembly factor 1) This gene encodes a transmembrane protein that is structurally similar to the mouse basic fibroblast growth factor repressed ZIC-binding protein. In mouse this protein may be involved in fibroblast growth factor regulated growth control. In humans, polymorphisms in this gene are associated with variation in human height and osteoarthritis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

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=0.051528484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCC1	NM_018244.5	c.152G>T	p.Arg51Leu	missense_variant	3/10	ENST00000374385.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCC1	ENST00000374385.10	c.152G>T	p.Arg51Leu	missense_variant	3/10	1	NM_018244.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460382 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 726488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.14
DANN	Benign	0.58
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.48	T;T;T;T;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.052	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N;.;N;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N;N;N;N;.;N;N
REVEL	Benign	0.031
Sift	Benign	0.31	T;T;T;T;.;T;T
Sift4G	Benign	0.21	T;T;T;T;T;.;T
Polyphen		0.0, 0.0010	.;.;.;B;.;.;B
Vest4		0.071
MutPred		0.33		Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);Loss of catalytic residue at R51 (P = 0.0062);.;.;Loss of catalytic residue at R51 (P = 0.0062);
MVP		0.072
MPC		0.36
ClinPred		0.18	T
GERP RS		-9.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4911494; hg19: chr20-33971914;