chr1-46315930-G-C

Variant names:

• chr1-46315930-G-C
• rs4660921
• NM_006004.4:c.244-622G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006004.4(UQCRH):​c.244-622G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRH	NM_006004.4	c.244-622G>C		intron_variant	Intron 3 of 3	ENST00000311672.10	NP_005995.2
UQCRH	NM_001297565.2	c.226-622G>C		intron_variant	Intron 4 of 4		NP_001284494.1
UQCRH	NM_001297566.2	c.217-622G>C		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>C		intron_variant	Intron 3 of 3	1	NM_006004.4	ENSP00000309565.5
UQCRH	ENST00000496387.5	n.*83-622G>C		intron_variant	Intron 4 of 4	1		ENSP00000477826.1
UQCRH	ENST00000460947.1	n.397-622G>C		intron_variant	Intron 1 of 1	2
UQCRH	ENST00000489056.5	n.*83-622G>C		intron_variant	Intron 3 of 3	2		ENSP00000484857.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		0.74

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;