20-35383282-A-G

Variant names:

• chr20-35383282-A-G
• rs6141548
• NM_018244.5:c.225+756T>C

Variant summary

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

The NM_018244.5(UQCC1):​c.225+756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,100 control chromosomes in the GnomAD database, including 23,447 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 0.54 (23447 hom., cov: 32)
• Consequence: UQCC1 NM_018244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 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.225+756T>C		intron	N/A	NP_060714.3
	UQCC1	NM_199487.3		c.225+756T>C		intron	N/A	NP_955781.2	Q9NVA1-2
	UQCC1	NM_001184977.2		c.130-9026T>C		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.225+756T>C		intron	N/A	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.123+10810T>C		intron	N/A	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000491040.5	TSL:1	n.*108-1257T>C		intron	N/A	ENSP00000420584.1	D6RDV2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82560 AN: 151984 Hom.: 23441 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.543 AC: 82570 AN: 152100 Hom.: 23447 Cov.: 32 AF XY: 0.541 AC XY: 40250 AN XY: 74350

African (AFR) AF: 0.365 AC: 15141 AN: 41470

American (AMR) AF: 0.649 AC: 9921 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1926 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3715 AN: 5186

South Asian (SAS) AF: 0.443 AC: 2136 AN: 4820

European-Finnish (FIN) AF: 0.573 AC: 6050 AN: 10560

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

European-Non Finnish (NFE) AF: 0.615 AC: 41796 AN: 67996

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.518 Hom.: 7067

Bravo AF: 0.549

Asia WGS AF: 0.483 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.42
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: rs6141548; hg19: chr20-33971085;