15-41417234-C-A

Variant summary

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

The NM_015138.5(RTF1):​c.119C>A​(p.Thr40Asn) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RTF1
NM_015138.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41
Variant links:
Genes affected
RTF1 (HGNC:28996): (RTF1 homolog, Paf1/RNA polymerase II complex component) This locus may represent a gene involved in regulation of transcription elongation and chromatin remodeling, based on studies of similar proteins in other organisms. The encoded protein may bind single-stranded DNA. [provided by RefSeq, Sep 2010]

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=0.11544627).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTF1NM_015138.5 linkc.119C>A p.Thr40Asn missense_variant Exon 1 of 18 ENST00000389629.9 NP_055953.3 Q92541

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTF1ENST00000389629.9 linkc.119C>A p.Thr40Asn missense_variant Exon 1 of 18 1 NM_015138.5 ENSP00000374280.4 Q92541
RTF1ENST00000462276.1 linkn.103C>A non_coding_transcript_exon_variant Exon 1 of 4 4
RTF1ENST00000558298.5 linkn.174+8653C>A intron_variant Intron 1 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1103660
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
523126
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.119C>A (p.T40N) alteration is located in exon 1 (coding exon 1) of the RTF1 gene. This alteration results from a C to A substitution at nucleotide position 119, causing the threonine (T) at amino acid position 40 to be replaced by an asparagine (N). 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
0.14
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.068
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.49
T
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.26
N
REVEL
Benign
0.060
Sift
Benign
0.039
D
Sift4G
Benign
0.46
T
Polyphen
0.063
B
Vest4
0.12
MutPred
0.26
Loss of sheet (P = 0.0037);
MVP
0.23
MPC
1.4
ClinPred
0.78
D
GERP RS
3.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.17
gMVP
0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41709432; API