20-35394112-C-T

Variant names:

• chr20-35394112-C-T
• rs1019129354
• NM_018244.5:c.109G>A

Variant summary

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

The NM_018244.5(UQCC1):​c.109G>A​(p.Ala37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=0.037067384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCC1	NM_018244.5	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 10	ENST00000374385.10	NP_060714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCC1	ENST00000374385.10	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 10	1	NM_018244.5	ENSP00000363506.5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461694 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727176

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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 AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74282

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.7
DANN	Benign	0.67
DEOGEN2	Benign	0.0063	.;T;.;.;T;T;T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T;T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.037	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N;.;N;N;N;.;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.49	N;N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.56	T;T;T;T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T;.;.;T
Polyphen		0.0	.;.;.;.;B;.;.;.
Vest4		0.13
MutPred		0.27		Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);Gain of phosphorylation at A37 (P = 0.0153);
MVP		0.31
MPC		0.28
ClinPred		0.023	T
GERP RS		-0.0083
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs1019129354; hg19: chr20-33981915;