rs745399167

Variant names:

• chr3-48599668-T-A
• rs745399167
• NM_003365.3:c.1345A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-48599668-T-A
• chr3-48599668-T-C
• chr3-48599668-T-G

Variant summary

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

The NM_003365.3(UQCRC1):​c.1345A>T​(p.Ile449Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCRC1 NM_003365.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

Genes affected

UQCRC1 (HGNC:12585): (ubiquinol-cytochrome c reductase core protein 1) Enables ubiquitin protein ligase binding activity. Predicted to be involved in oxidative phosphorylation. Predicted to act upstream of or within mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrion. Implicated in Alzheimer's disease. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23694295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRC1	NM_003365.3	c.1345A>T	p.Ile449Phe	missense_variant	Exon 12 of 13	ENST00000203407.6	NP_003356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRC1	ENST00000203407.6	c.1345A>T	p.Ile449Phe	missense_variant	Exon 12 of 13	1	NM_003365.3	ENSP00000203407.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.76
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.59		Loss of methylation at K447 (P = 0.0704);
MVP		0.19
MPC		0.35
ClinPred		0.33	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs745399167; hg19: chr3-48637101;