rs10420904

Variant names:

• chr19-29212182-C-T
• rs10420904
• NM_006003.3:c.214+723G>A

Variant summary

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

The NM_006003.3(UQCRFS1):​c.214+723G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,978 control chromosomes in the GnomAD database, including 18,748 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 0.48 (18748 hom., cov: 32)
• Consequence: UQCRFS1 NM_006003.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 8 publications found

Genes affected

UQCRFS1 (HGNC:12587): (ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1) Predicted to enable oxidoreductase activity. Involved in mitochondrial respiratory chain complex III assembly and respiratory electron transport chain. Located in mitochondrion. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. Implicated in mitochondrial complex III deficiency. [provided by Alliance of Genome Resources, Apr 2022]

UQCRFS1 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex III deficiency, nuclear type 10

  Inheritance: AR 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRFS1	NM_006003.3	c.214+723G>A		intron_variant	Intron 1 of 1	ENST00000304863.6	NP_005994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRFS1	ENST00000304863.6	c.214+723G>A		intron_variant	Intron 1 of 1	1	NM_006003.3	ENSP00000306397.3

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72769 AN: 151860 Hom.: 18720 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.479 AC: 72857 AN: 151978 Hom.: 18748 Cov.: 32 AF XY: 0.478 AC XY: 35495 AN XY: 74268

African (AFR) AF: 0.677 AC: 28058 AN: 41460

American (AMR) AF: 0.467 AC: 7135 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1577 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2668 AN: 5142

South Asian (SAS) AF: 0.468 AC: 2256 AN: 4820

European-Finnish (FIN) AF: 0.350 AC: 3689 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.383 AC: 26015 AN: 67952

Other (OTH) AF: 0.500 AC: 1055 AN: 2110

Alfa AF: 0.444 Hom.: 3348

Bravo AF: 0.493

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.31
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: rs10420904; hg19: chr19-29703089;