NM_018244.5:c.496C>T

Variant names:

• chr20-35347241-G-A
• rs143345851
• NM_018244.5:c.496C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018244.5(UQCC1):​c.496C>T​(p.Arg166Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000564 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• Publications: 6 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: Uncertain_significance. The variant received 0 ACMG points.

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.496C>T	p.Arg166Trp	missense	Exon 7 of 10	NP_060714.3
	UQCC1	NM_199487.3		c.496C>T	p.Arg166Trp	missense	Exon 7 of 9	NP_955781.2	Q9NVA1-2
	UQCC1	NM_001184977.2		c.292C>T	p.Arg98Trp	missense	Exon 5 of 8	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.496C>T	p.Arg166Trp	missense	Exon 7 of 10	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.*48C>T		non_coding_transcript_exon	Exon 4 of 7	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000491040.5	TSL:1	n.*378C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000420584.1	D6RDV2

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

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: 0.000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000219 AC: 55 AN: 250940 AF XY: 0.000214

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000424

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000594 AC: 868 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.000546 AC XY: 397 AN XY: 727236

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000740 AC: 823 AN: 1112002

Other (OTH) AF: 0.000613 AC: 37 AN: 60396

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74240

African (AFR) AF: 0.000266 AC: 11 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68004

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000490 Hom.: 0

Bravo AF: 0.000283

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.85
MVP		0.69
MPC		1.0
ClinPred		0.82	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.54
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs143345851; hg19: chr20-33935044; COSMIC: COSV62902692; COSMIC: COSV62902692;