rs703657

Positions:

• chr12-103957073-T-A

Variant summary

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

The NM_001135570.3(UQCC6):​c.-15A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 329,302 control chromosomes in the GnomAD database, including 24,455 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 0.40 (13353 hom., cov: 32)
  • Exomes 𝑓: 0.34 (11102 hom.)
• Consequence: UQCC6 NM_001135570.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCC6	NM_001135570.3	c.-15A>T		5_prime_UTR_variant	1/3	ENST00000378090.9
UQCC6	XM_011538718.4	c.-942A>T		5_prime_UTR_variant	1/5
UQCC6	XM_017019916.3	c.-11+67A>T		intron_variant
UQCC6	XM_017019917.3	c.-10-325A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCC6	ENST00000378090.9	c.-15A>T		5_prime_UTR_variant	1/3	1	NM_001135570.3	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61092 AN: 151966 Hom.: 13338 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.343 AC: 60861 AN: 177218 Hom.: 11102 Cov.: 0 AF XY: 0.342 AC XY: 31962 AN XY: 93492

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.402 AC: 61150 AN: 152084 Hom.: 13353 Cov.: 32 AF XY: 0.400 AC XY: 29730 AN XY: 74318

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.392

Alfa AF: 0.365 Hom.: 1319

Bravo AF: 0.422

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs703657; hg19: chr12-104350851;