19-29213103-A-G

Variant names:

• chr19-29213103-A-G
• rs8100724
• NM_006003.3:c.16T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006003.3(UQCRFS1):​c.16T>C​(p.Ser6Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UQCRFS1 NM_006003.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661

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-DT (HGNC:55295): (UQCRFS1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1286535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRFS1	NM_006003.3	c.16T>C	p.Ser6Pro	missense_variant	Exon 1 of 2	ENST00000304863.6	NP_005994.2
UQCRFS1-DT	NR_184021.1	n.-150A>G		upstream_gene_variant
UQCRFS1-DT	NR_184022.1	n.-150A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRFS1	ENST00000304863.6	c.16T>C	p.Ser6Pro	missense_variant	Exon 1 of 2	1	NM_006003.3	ENSP00000306397.3
UQCRFS1-DT	ENST00000587859.1	n.-132A>G		upstream_gene_variant		2
UQCRFS1-DT	ENST00000590607.2	n.-180A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000220 AC: 3 AN: 1363846 Hom.: 0 Cov.: 50 AF XY: 0.00000297 AC XY: 2 AN XY: 673084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000280

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.064
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.059	T
Polyphen		0.051	B
Vest4		0.090
MutPred		0.49		Loss of phosphorylation at S6 (P = 0.0309);
MVP		0.15
MPC		1.5
ClinPred		0.61	D
GERP RS		-0.080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs8100724; hg19: chr19-29704010;