rs1047490

Variant names:

• chr12-103951278-G-A
• rs1047490
• ENST00000543740.6:n.654C>T

Variant summary

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

The ENST00000543740.6(UQCC6):​n.654C>T variant causes a non coding transcript exon 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 ENST00000543740.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 7 publications found

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

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 = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000543740.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC6	NM_001135570.3	MANE Select	c.*245C>T		3_prime_UTR	Exon 3 of 3	NP_001129042.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC6	ENST00000543740.6	TSL:1	n.654C>T		non_coding_transcript_exon	Exon 3 of 3
	UQCC6	ENST00000378090.9	TSL:1 MANE Select	c.*245C>T		3_prime_UTR	Exon 3 of 3	ENSP00000367330.4
	UQCC6	ENST00000549478.1	TSL:1	c.*245C>T		3_prime_UTR	Exon 2 of 2	ENSP00000448771.1

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

African (AFR) AF: 0.650 AC: 3734 AN: 5744

American (AMR) AF: 0.607 AC: 3812 AN: 6284

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 4344 AN: 7264

East Asian (EAS) AF: 0.992 AC: 16204 AN: 16332

South Asian (SAS) AF: 0.594 AC: 2619 AN: 4408

European-Finnish (FIN) AF: 0.512 AC: 6286 AN: 12286

Middle Eastern (MID) AF: 0.632 AC: 613 AN: 970

European-Non Finnish (NFE) AF: 0.508 AC: 61936 AN: 121932

Other (OTH) AF: 0.571 AC: 7043 AN: 12334

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

African (AFR) AF: 0.655 AC: 27170 AN: 41466

American (AMR) AF: 0.601 AC: 9178 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2114 AN: 3472

East Asian (EAS) AF: 0.990 AC: 5135 AN: 5186

South Asian (SAS) AF: 0.602 AC: 2904 AN: 4826

European-Finnish (FIN) AF: 0.524 AC: 5521 AN: 10528

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34385 AN: 67942

Other (OTH) AF: 0.561 AC: 1185 AN: 2112

Alfa AF: 0.567 Hom.: 12089

Bravo AF: 0.592

Asia WGS AF: 0.773 AC: 2687 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	5.1
DANN	Benign	0.48
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1047490; hg19: chr12-104345056;