19-29212968-T-C

Variant names:

• chr19-29212968-T-C
• rs993154172
• NM_006003.3:c.151A>G

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.151A>G​(p.Ser51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S51C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: UQCRFS1 NM_006003.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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-DT (HGNC:55295): (UQCRFS1 divergent transcript)

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=0.15771773).

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.151A>G	p.Ser51Gly	missense	Exon 1 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.151A>G	p.Ser51Gly	missense	Exon 1 of 2	ENSP00000306397.3	P47985
	UQCRFS1	ENST00000933914.1		c.151A>G	p.Ser51Gly	missense	Exon 1 of 2	ENSP00000603973.1
	UQCRFS1-DT	ENST00000587859.2	TSL:2	n.-240T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.01e-7 AC: 1 AN: 1248554 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 608702

African (AFR) AF: 0.0000417 AC: 1 AN: 23966

American (AMR) AF: 0.00 AC: 0 AN: 12482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17712

East Asian (EAS) AF: 0.00 AC: 0 AN: 28066

South Asian (SAS) AF: 0.00 AC: 0 AN: 59150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022176

Other (OTH) AF: 0.00 AC: 0 AN: 51590

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.066
Sift	Benign	0.21	T
Sift4G	Benign	0.35	T
Polyphen		0.074	B
Vest4		0.095
MutPred		0.62		Loss of phosphorylation at S51 (P = 0.0413)
MVP		0.21
MPC		1.1
ClinPred		0.38	T
GERP RS		0.76
PromoterAI		0.0030	Neutral
Varity_R		0.33
gMVP		0.48
Mutation Taster		=95/5	polymorphism

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: rs993154172; hg19: chr19-29703875;