NM_018244.5:c.590T>C

Variant names:

• chr20-35314749-A-G
• rs199898677
• NM_018244.5:c.590T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018244.5(UQCC1):​c.590T>C​(p.Leu197Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. L197Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• Publications: 0 publications found

Genes affected

UQCC1 (HGNC:15891): (ubiquinol-cytochrome c reductase complex assembly factor 1) This gene encodes a transmembrane protein that is structurally similar to the mouse basic fibroblast growth factor repressed ZIC-binding protein. In mouse this protein may be involved in fibroblast growth factor regulated growth control. In humans, polymorphisms in this gene are associated with variation in human height and osteoarthritis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018244.5. 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
	UQCC1	NM_018244.5	MANE Select	c.590T>C	p.Leu197Pro	missense	Exon 8 of 10	NP_060714.3
	UQCC1	NM_001184977.2		c.386T>C	p.Leu129Pro	missense	Exon 6 of 8	NP_001171906.1	Q9NVA1-5
	UQCC1	NM_199487.3		c.574-7970T>C		intron	N/A	NP_955781.2	Q9NVA1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC1	ENST00000374385.10	TSL:1 MANE Select	c.590T>C	p.Leu197Pro	missense	Exon 8 of 10	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.*142T>C		non_coding_transcript_exon	Exon 5 of 7	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000457259.5	TSL:1	n.*142T>C		3_prime_UTR	Exon 5 of 7	ENSP00000411024.1	H7C3C3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.34
Sift	Benign	0.079	T
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.84		Loss of stability (P = 0.0184)
MVP		0.79
MPC		1.2
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.84
gMVP		0.85
Mutation Taster		=58/42	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: rs199898677; hg19: chr20-33902552;