20-35381959-C-T

Variant names:

• chr20-35381959-C-T
• NM_018244.5:c.292G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018244.5(UQCC1):​c.292G>A​(p.Glu98Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCC1	NM_018244.5	c.292G>A	p.Glu98Lys	missense_variant	Exon 4 of 10	ENST00000374385.10	NP_060714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCC1	ENST00000374385.10	c.292G>A	p.Glu98Lys	missense_variant	Exon 4 of 10	1	NM_018244.5	ENSP00000363506.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726712

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.292G>A (p.E98K) alteration is located in exon 4 (coding exon 4) of the UQCC1 gene. This alteration results from a G to A substitution at nucleotide position 292, causing the glutamic acid (E) at amino acid position 98 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.042	.;T;.;T;T;T;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.6	L;.;L;L;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.91	N;N;N;N;.;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.11	T;D;T;T;.;T;T;T
Sift4G	Benign	0.25	T;D;T;T;T;.;.;T
Polyphen		0.039, 0.22	.;.;.;B;.;.;.;B
Vest4		0.59
MutPred		0.52		Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);Gain of MoRF binding (P = 0.0034);.;.;.;Gain of MoRF binding (P = 0.0034);
MVP		0.44
MPC		0.39
ClinPred		0.85	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33969762;