NM_025065.7:c.107C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025065.7(RPF1):​c.107C>T​(p.Thr36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RPF1
NM_025065.7 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.490
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08568129).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPF1NM_025065.7 linkc.107C>T p.Thr36Met missense_variant Exon 1 of 9 ENST00000370654.6 NP_079341.2 Q9H9Y2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPF1ENST00000370654.6 linkc.107C>T p.Thr36Met missense_variant Exon 1 of 9 1 NM_025065.7 ENSP00000359688.5 Q9H9Y2
RPF1ENST00000370656.5 linkc.107C>T p.Thr36Met missense_variant Exon 1 of 3 2 ENSP00000359690.1 X6R7Q1
ENSG00000285361ENST00000644783.1 linkn.*231C>T downstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152252
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251026
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461814
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152370
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.107C>T (p.T36M) alteration is located in exon 1 (coding exon 1) of the RPF1 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the threonine (T) at amino acid position 36 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0060
.;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.086
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.086
Sift
Uncertain
0.023
D;T
Sift4G
Benign
0.10
T;T
Polyphen
0.0050
.;B
Vest4
0.25
MutPred
0.20
Loss of glycosylation at T36 (P = 0.0112);Loss of glycosylation at T36 (P = 0.0112);
MVP
0.54
MPC
0.18
ClinPred
0.20
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.076
gMVP
0.16

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs557621729; hg19: chr1-84945071; API