rs1047490

Positions:

• chr12-103951278-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135570.3(UQCC6):​c.*245C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 339,562 control chromosomes in the GnomAD database, including 58,793 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 0.58 (26523 hom., cov: 33)
  • Exomes 𝑓: 0.57 (32270 hom.)
• Consequence: UQCC6 NM_001135570.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

UQCC6 (HGNC:34450): (ubiquinol-cytochrome c reductase complex assembly factor 6) Involved in mitochondrial respiratory chain complex III assembly. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSP90B1 (HGNC:12028): (heat shock protein 90 beta family member 1) This gene encodes a member of a family of adenosine triphosphate(ATP)-metabolizing molecular chaperones with roles in stabilizing and folding other proteins. The encoded protein is localized to melanosomes and the endoplasmic reticulum. Expression of this protein is associated with a variety of pathogenic states, including tumor formation. There is a microRNA gene located within the 5' exon of this gene. There are pseudogenes for this gene on chromosomes 1 and 15. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -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 = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC6	NM_001135570.3	c.*245C>T		3_prime_UTR_variant	3/3	ENST00000378090.9	NP_001129042.1
UQCC6	XM_011538718.4	c.*245C>T		3_prime_UTR_variant	5/5		XP_011537020.1
UQCC6	XM_017019916.3	c.*245C>T		3_prime_UTR_variant	3/3		XP_016875405.1
UQCC6	XM_017019917.3	c.*245C>T		3_prime_UTR_variant	3/3		XP_016875406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCC6	ENST00000378090.9	c.*245C>T		3_prime_UTR_variant	3/3	1	NM_001135570.3	ENSP00000367330	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88230 AN: 151890 Hom.: 26501 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.568 AC: 106591 AN: 187554 Hom.: 32270 Cov.: 0 AF XY: 0.567 AC XY: 54497 AN XY: 96140

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.581 AC: 88309 AN: 152008 Hom.: 26523 Cov.: 33 AF XY: 0.585 AC XY: 43497 AN XY: 74304

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.561

Alfa AF: 0.549 Hom.: 5715

Bravo AF: 0.592

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047490; hg19: chr12-104345056;