1-46315930-G-T

Variant names:

• chr1-46315930-G-T
• rs4660921
• NM_006004.4:c.244-622G>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.244-622G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,956 control chromosomes in the GnomAD database, including 34,343 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 0.66 (34343 hom., cov: 32)
• Consequence: UQCRH NM_006004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 6 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 = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRH	NM_006004.4	c.244-622G>T		intron_variant	Intron 3 of 3	ENST00000311672.10	NP_005995.2
UQCRH	NM_001297565.2	c.226-622G>T		intron_variant	Intron 4 of 4		NP_001284494.1
UQCRH	NM_001297566.2	c.217-622G>T		intron_variant	Intron 2 of 2		NP_001284495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRH	ENST00000311672.10	c.244-622G>T		intron_variant	Intron 3 of 3	1	NM_006004.4	ENSP00000309565.5
UQCRH	ENST00000496387.5	n.*83-622G>T		intron_variant	Intron 4 of 4	1		ENSP00000477826.1
UQCRH	ENST00000460947.1	n.397-622G>T		intron_variant	Intron 1 of 1	2
UQCRH	ENST00000489056.5	n.*83-622G>T		intron_variant	Intron 3 of 3	2		ENSP00000484857.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100621 AN: 151838 Hom.: 34336 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.663 AC: 100676 AN: 151956 Hom.: 34343 Cov.: 32 AF XY: 0.662 AC XY: 49139 AN XY: 74274

African (AFR) AF: 0.486 AC: 20123 AN: 41390

American (AMR) AF: 0.675 AC: 10299 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2786 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4080 AN: 5176

South Asian (SAS) AF: 0.695 AC: 3349 AN: 4816

European-Finnish (FIN) AF: 0.666 AC: 7028 AN: 10558

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50579 AN: 67982

Other (OTH) AF: 0.694 AC: 1461 AN: 2106

Alfa AF: 0.729 Hom.: 49480

Bravo AF: 0.656

Asia WGS AF: 0.736 AC: 2555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.71
PhyloP100		0.74
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: rs4660921; hg19: chr1-46781602;