NM_018244.5:c.152G>A

Variant names:

• chr20-35384111-C-T
• rs4911494
• NM_018244.5:c.152G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.150
• Publications: 78 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1245347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018244.5. 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
	UQCC1	NM_018244.5	MANE Select	c.152G>A	p.Arg51Gln	missense	Exon 3 of 10	NP_060714.3
	UQCC1	NM_199487.3		c.152G>A	p.Arg51Gln	missense	Exon 3 of 9	NP_955781.2	Q9NVA1-2
	UQCC1	NM_001184977.2		c.130-9855G>A		intron	N/A	NP_001171906.1	Q9NVA1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC1	ENST00000374385.10	TSL:1 MANE Select	c.152G>A	p.Arg51Gln	missense	Exon 3 of 10	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.123+9981G>A		intron	N/A	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000491040.5	TSL:1	n.*108-2086G>A		intron	N/A	ENSP00000420584.1	D6RDV2

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

GnomAD2 exomes AF: 0.589 AC: 147843 AN: 251060 AF XY: 0.581

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 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

African (AFR) AF: 0.352 AC: 11762 AN: 33424

American (AMR) AF: 0.730 AC: 32595 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 14512 AN: 26044

East Asian (EAS) AF: 0.741 AC: 29392 AN: 39660

South Asian (SAS) AF: 0.441 AC: 38030 AN: 86166

European-Finnish (FIN) AF: 0.575 AC: 30636 AN: 53272

Middle Eastern (MID) AF: 0.516 AC: 2969 AN: 5750

European-Non Finnish (NFE) AF: 0.623 AC: 691638 AN: 1109452

Other (OTH) AF: 0.594 AC: 35784 AN: 60248

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

African (AFR) AF: 0.365 AC: 15130 AN: 41422

American (AMR) AF: 0.649 AC: 9910 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1925 AN: 3464

East Asian (EAS) AF: 0.717 AC: 3704 AN: 5166

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 6042 AN: 10570

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41770 AN: 67954

Other (OTH) AF: 0.558 AC: 1175 AN: 2104

Alfa AF: 0.590 Hom.: 102648

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.15
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.024
Sift	Benign	0.42	T
Sift4G	Benign	0.39	T
Polyphen		0.0	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
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs4911494; hg19: chr20-33971914; COSMIC: COSV107444720;