1-46314092-C-T

Variant names:

• chr1-46314092-C-T
• rs11588062
• NM_006004.4:c.244-2460C>T

Variant summary

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

The NM_006004.4(UQCRH):​c.244-2460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,968 control chromosomes in the GnomAD database, including 6,315 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 0.26 (6315 hom., cov: 32)
• Consequence: UQCRH NM_006004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 5 publications found

Genes affected

UQCRH (HGNC:12590): (ubiquinol-cytochrome c reductase hinge protein) Predicted to enable ubiquinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

UQCRH Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency, nuclear type 11

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006004.4. 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
	UQCRH	NM_006004.4	MANE Select	c.244-2460C>T		intron	N/A	NP_005995.2
	UQCRH	NM_001297565.2		c.226-2460C>T		intron	N/A	NP_001284494.1
	UQCRH	NM_001297566.2		c.217-2460C>T		intron	N/A	NP_001284495.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRH	ENST00000311672.10	TSL:1 MANE Select	c.244-2460C>T		intron	N/A	ENSP00000309565.5
	UQCRH	ENST00000496387.5	TSL:1	n.*83-2460C>T		intron	N/A	ENSP00000477826.1
	UQCRH	ENST00000460947.1	TSL:2	n.397-2460C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39560 AN: 151850 Hom.: 6322 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.260 AC: 39549 AN: 151968 Hom.: 6315 Cov.: 32 AF XY: 0.260 AC XY: 19319 AN XY: 74244

African (AFR) AF: 0.0812 AC: 3368 AN: 41460

American (AMR) AF: 0.356 AC: 5430 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1514 AN: 3472

East Asian (EAS) AF: 0.479 AC: 2474 AN: 5168

South Asian (SAS) AF: 0.201 AC: 967 AN: 4812

European-Finnish (FIN) AF: 0.262 AC: 2760 AN: 10540

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21906 AN: 67950

Other (OTH) AF: 0.289 AC: 610 AN: 2108

Alfa AF: 0.283 Hom.: 1696

Bravo AF: 0.263

Asia WGS AF: 0.348 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.85
DANN	Benign	0.80
PhyloP100		0.10
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: rs11588062; hg19: chr1-46779764; COSMIC: COSV61176074; COSMIC: COSV61176074;