1-84479476-A-C

Variant names:

• chr1-84479476-A-C
• NM_025065.7:c.195A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025065.7(RPF1):​c.195A>C​(p.Leu65Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPF1 NM_025065.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.325
• Publications: 0 publications found

Genes affected

RPF1 (HGNC:30350): (ribosome production factor 1 homolog) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09009597).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025065.7. 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
	RPF1	NM_025065.7	MANE Select	c.195A>C	p.Leu65Phe	missense	Exon 1 of 9	NP_079341.2	Q9H9Y2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPF1	ENST00000370654.6	TSL:1 MANE Select	c.195A>C	p.Leu65Phe	missense	Exon 1 of 9	ENSP00000359688.5	Q9H9Y2
	RPF1	ENST00000923273.1		c.195A>C	p.Leu65Phe	missense	Exon 1 of 9	ENSP00000593332.1
	RPF1	ENST00000953136.1		c.195A>C	p.Leu65Phe	missense	Exon 1 of 9	ENSP00000623195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461830 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.33
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.042
Sift	Benign	0.35	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.36		Gain of helix (P = 0.0078)
MVP		0.48
MPC		0.14
ClinPred		0.24	T
GERP RS		-3.5
PromoterAI		0.097	Neutral
Varity_R		0.10
gMVP		0.062
Mutation Taster		=73/27	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

hg19: chr1-84945159;