20-35384111-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018244.5(UQCC1):c.152G>A(p.Arg51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,610,670 control chromosomes in the GnomAD database, including 297,383 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (23427 hom., cov: 32)
  • Exomes 𝑓: 0.61 (273956 hom.)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5950916E-6).
• BP6: Variant 20-35384111-C-T is Benign according to our data. Variant chr20-35384111-C-T is described in ClinVar as [Benign]. Clinvar id is 1245347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCC1	NM_018244.5	c.152G>A	p.Arg51Gln	missense_variant	3/10	ENST00000374385.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCC1	ENST00000374385.10	c.152G>A	p.Arg51Gln	missense_variant	3/10	1	NM_018244.5	P1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82488 AN: 151866 Hom.: 23421 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.565

GnomAD3 exomes AF: 0.589 AC: 147843 AN: 251060 Hom.: 45023 AF XY: 0.581 AC XY: 78812 AN XY: 135714

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.741

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.713

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.608 AC: 887318 AN: 1458686 Hom.: 273956 Cov.: 40 AF XY: 0.603 AC XY: 437287 AN XY: 725732

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.730

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.543 AC: 82499 AN: 151984 Hom.: 23427 Cov.: 32 AF XY: 0.541 AC XY: 40227 AN XY: 74308

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.558

Alfa AF: 0.598 Hom.: 71108

Bravo AF: 0.548

TwinsUK AF: 0.620 AC: 2298

ALSPAC AF: 0.633 AC: 2439

ESP6500AA AF: 0.366 AC: 1612

ESP6500EA AF: 0.608 AC: 5226

ExAC AF: 0.577 AC: 70058

Asia WGS AF: 0.483 AC: 1681 AN: 3478

EpiCase AF: 0.612

EpiControl AF: 0.601

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 19343178) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.30
Dann	Benign	0.62
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.33	T;T;T;T;T;T;T
MetaRNN	Benign	0.0000016	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.60	N;.;N;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.84	N;N;N;N;.;N;N
REVEL	Benign	0.024
Sift	Benign	0.42	T;T;T;T;.;T;T
Sift4G	Benign	0.39	T;T;T;T;T;.;T
Polyphen		0.0, 0.022	.;.;.;B;.;.;B
Vest4		0.024
MPC		0.33
ClinPred		0.028	T
GERP RS		-9.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.012
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;