chr6-33697848-C-T

Variant names:

• chr6-33697848-C-T
• rs112204790
• NM_032340.4:c.284-98G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032340.4(UQCC2):​c.284-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 938,254 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (4 hom.)
• Consequence: UQCC2 NM_032340.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31
• Publications: 0 publications found

Genes affected

UQCC2 (HGNC:21237): (ubiquinol-cytochrome c reductase complex assembly factor 2) This gene encodes a nucleoid protein localized to the mitochondria inner membrane. The encoded protein affects regulation of insulin secretion, mitochondrial ATP production, and myogenesis through modulation of mitochondrial respiratory chain activity. [provided by RefSeq, Oct 2012]

UQCC2 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex III deficiency nuclear type 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-33697848-C-T is Benign according to our data. Variant chr6-33697848-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1194865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0057 (868/152298) while in subpopulation AFR AF = 0.0196 (814/41592). AF 95% confidence interval is 0.0185. There are 14 homozygotes in GnomAd4. There are 433 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032340.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC2	NM_032340.4	MANE Select	c.284-98G>A		intron	N/A	NP_115716.1	Q9BRT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC2	ENST00000607484.6	TSL:1 MANE Select	c.284-98G>A		intron	N/A	ENSP00000476140.1	Q9BRT2
	UQCC2	ENST00000931724.1		c.392-98G>A		intron	N/A	ENSP00000601783.1
	UQCC2	ENST00000887985.1		c.284-98G>A		intron	N/A	ENSP00000558044.1

Frequencies

GnomAD3 genomes AF: 0.00572 AC: 870 AN: 152180 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000629 AC: 494 AN: 785956 Hom.: 4 Cov.: 10 AF XY: 0.000552 AC XY: 225 AN XY: 407242

African (AFR) AF: 0.0182 AC: 355 AN: 19472

American (AMR) AF: 0.00212 AC: 58 AN: 27348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17408

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.0000856 AC: 5 AN: 58394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37770

Middle Eastern (MID) AF: 0.000471 AC: 2 AN: 4246

European-Non Finnish (NFE) AF: 0.0000274 AC: 15 AN: 547800

Other (OTH) AF: 0.00156 AC: 59 AN: 37822

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152298 Hom.: 14 Cov.: 33 AF XY: 0.00581 AC XY: 433 AN XY: 74472

African (AFR) AF: 0.0196 AC: 814 AN: 41592

American (AMR) AF: 0.00275 AC: 42 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67974

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00710 Hom.: 2

Bravo AF: 0.00669

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.16
DANN	Benign	0.72
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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: rs112204790; hg19: chr6-33665625;