NM_006003.3:c.631G>C

Variant names:

• chr19-29207742-C-G
• rs1599710159
• NM_006003.3:c.631G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006003.3(UQCRFS1):​c.631G>C​(p.Val211Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UQCRFS1 NM_006003.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101044536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006003.3. 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
	UQCRFS1	NM_006003.3	MANE Select	c.631G>C	p.Val211Leu	missense	Exon 2 of 2	NP_005994.2	P47985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRFS1	ENST00000304863.6	TSL:1 MANE Select	c.631G>C	p.Val211Leu	missense	Exon 2 of 2	ENSP00000306397.3	P47985
	UQCRFS1	ENST00000933914.1		c.601G>C	p.Val201Leu	missense	Exon 2 of 2	ENSP00000603973.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.31
DANN	Benign	0.16
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.9	N
PhyloP100		0.65
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.52		Loss of sheet (P = 0.0817)
MVP		0.57
MPC		1.1
ClinPred		0.039	T
GERP RS		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.80
Mutation Taster		=50/50

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: rs1599710159; hg19: chr19-29698649;