20-35394112-C-T

Variant names:

• chr20-35394112-C-T
• rs1019129354
• NM_018244.5:c.109G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018244.5(UQCC1):​c.109G>A​(p.Ala37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UQCC1 NM_018244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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: 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 (MetaRNN=0.037067384).

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.109G>A	p.Ala37Thr	missense	Exon 2 of 10	NP_060714.3
	UQCC1	NM_199487.3		c.109G>A	p.Ala37Thr	missense	Exon 2 of 9	NP_955781.2	Q9NVA1-2
	UQCC1	NM_001184977.2		c.109G>A	p.Ala37Thr	missense	Exon 2 of 8	NP_001171906.1	Q9NVA1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC1	ENST00000374385.10	TSL:1 MANE Select	c.109G>A	p.Ala37Thr	missense	Exon 2 of 10	ENSP00000363506.5	Q9NVA1-1
	UQCC1	ENST00000457259.5	TSL:1	n.103G>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000411024.1	H7C3C3
	UQCC1	ENST00000491040.5	TSL:1	n.109G>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000420584.1	D6RDV2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461694 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727176

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74282

African (AFR) AF: 0.0000483 AC: 2 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.7
DANN	Benign	0.67
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.033
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.22
Sift	Benign	0.56	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.27		Gain of phosphorylation at A37 (P = 0.0153)
MVP		0.31
MPC		0.28
ClinPred		0.023	T
GERP RS		-0.0083
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.22
Mutation Taster		=94/6	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: rs1019129354; hg19: chr20-33981915;