chr12-103961021-T-C

Variant names:

• chr12-103961021-T-C
• rs812498
• ENST00000543740.6:n.180+4495A>G

Variant summary

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

The ENST00000543740.6(UQCC6):​n.180+4495A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,930 control chromosomes in the GnomAD database, including 4,077 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 0.23 (4077 hom., cov: 31)
• Consequence: UQCC6 ENST00000543740.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC6	ENST00000543740.6	TSL:1	n.180+4495A>G		intron	N/A
	UQCC6	ENST00000553183.5	TSL:3	c.-10-4273A>G		intron	N/A	ENSP00000446981.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34319 AN: 151812 Hom.: 4072 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.226 AC: 34337 AN: 151930 Hom.: 4077 Cov.: 31 AF XY: 0.226 AC XY: 16786 AN XY: 74242

African (AFR) AF: 0.231 AC: 9582 AN: 41396

American (AMR) AF: 0.304 AC: 4639 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3466

East Asian (EAS) AF: 0.310 AC: 1604 AN: 5170

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4810

European-Finnish (FIN) AF: 0.184 AC: 1940 AN: 10532

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13726 AN: 67974

Other (OTH) AF: 0.226 AC: 476 AN: 2104

Alfa AF: 0.213 Hom.: 14696

Bravo AF: 0.236

Asia WGS AF: 0.269 AC: 936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs812498; hg19: chr12-104354799;