rs4660921

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-46315930-G-C
• chr1-46315930-G-T

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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRH	NM_006004.4	MANE Select	c.244-622G>C		intron	N/A	NP_005995.2
	UQCRH	NM_001297565.2		c.226-622G>C		intron	N/A	NP_001284494.1
	UQCRH	NM_001297566.2		c.217-622G>C		intron	N/A	NP_001284495.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRH	ENST00000311672.10	TSL:1 MANE Select	c.244-622G>C		intron	N/A	ENSP00000309565.5
	UQCRH	ENST00000496387.5	TSL:1	n.*83-622G>C		intron	N/A	ENSP00000477826.1
	UQCRH	ENST00000912001.1		c.382-622G>C		intron	N/A	ENSP00000582060.1

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 v4.9

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;