12-103957073-T-A

Variant names:

• chr12-103957073-T-A
• rs703657
• NM_001135570.3:c.-15A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135570.3. 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.-15A>T		5_prime_UTR	Exon 1 of 3	NP_001129042.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC6	ENST00000378090.9	TSL:1 MANE Select	c.-15A>T		5_prime_UTR	Exon 1 of 3	ENSP00000367330.4
	UQCC6	ENST00000549478.1	TSL:1	c.-335A>T		5_prime_UTR	Exon 1 of 2	ENSP00000448771.1
	UQCC6	ENST00000543740.6	TSL:1	n.181-3539A>T		intron	N/A

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

African (AFR) AF: 0.565 AC: 3357 AN: 5942

American (AMR) AF: 0.445 AC: 3793 AN: 8516

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 2196 AN: 5242

East Asian (EAS) AF: 0.468 AC: 4445 AN: 9502

South Asian (SAS) AF: 0.349 AC: 8593 AN: 24656

European-Finnish (FIN) AF: 0.278 AC: 2641 AN: 9510

Middle Eastern (MID) AF: 0.450 AC: 353 AN: 784

European-Non Finnish (NFE) AF: 0.309 AC: 31811 AN: 102828

Other (OTH) AF: 0.359 AC: 3672 AN: 10238

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

African (AFR) AF: 0.566 AC: 23466 AN: 41480

American (AMR) AF: 0.438 AC: 6692 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1471 AN: 3460

East Asian (EAS) AF: 0.466 AC: 2411 AN: 5170

South Asian (SAS) AF: 0.334 AC: 1606 AN: 4812

European-Finnish (FIN) AF: 0.278 AC: 2937 AN: 10574

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21250 AN: 67990

Other (OTH) AF: 0.392 AC: 825 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		-1.2
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs703657; hg19: chr12-104350851;