rs725908

Variant names:

• chr20-35380264-T-C
• rs725908
• NM_018244.5:c.333+1654A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018244.5(UQCC1):​c.333+1654A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,008 control chromosomes in the GnomAD database, including 20,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (20901 hom., cov: 32)
• Consequence: UQCC1 NM_018244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.333+1654A>G		intron	N/A	NP_060714.3
	UQCC1	NM_199487.3		c.333+1654A>G		intron	N/A	NP_955781.2	Q9NVA1-2
	UQCC1	NM_001184977.2		c.130-6008A>G		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.333+1654A>G		intron	N/A	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.124-13650A>G		intron	N/A	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000491040.5	TSL:1	n.*215+1654A>G		intron	N/A	ENSP00000420584.1	D6RDV2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72852 AN: 151890 Hom.: 20898 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72847 AN: 152008 Hom.: 20901 Cov.: 32 AF XY: 0.480 AC XY: 35643 AN XY: 74302

African (AFR) AF: 0.146 AC: 6043 AN: 41484

American (AMR) AF: 0.626 AC: 9553 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1925 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3704 AN: 5182

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4824

European-Finnish (FIN) AF: 0.573 AC: 6018 AN: 10510

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41749 AN: 67962

Other (OTH) AF: 0.510 AC: 1074 AN: 2106

Alfa AF: 0.560 Hom.: 40431

Bravo AF: 0.477

Asia WGS AF: 0.472 AC: 1632 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs725908; hg19: chr20-33968067;